TY - JOUR
AB - The plant-signaling molecule auxin triggers fast and slow cellular responses across land plants and algae. The nuclear auxin pathway mediates gene expression and controls growth and development in land plants, but this pathway is absent from algal sister groups. Several components of rapid responses have been identified in Arabidopsis, but it is unknown if these are part of a conserved mechanism. We recently identified a fast, proteome-wide phosphorylation response to auxin. Here, we show that this response occurs across 5 land plant and algal species and converges on a core group of shared targets. We found conserved rapid physiological responses to auxin in the same species and identified rapidly accelerated fibrosarcoma (RAF)-like protein kinases as central mediators of auxin-triggered phosphorylation across species. Genetic analysis connects this kinase to both auxin-triggered protein phosphorylation and rapid cellular response, thus identifying an ancient mechanism for fast auxin responses in the green lineage.
AU - Kuhn, Andre
AU - Roosjen, Mark
AU - Mutte, Sumanth
AU - Dubey, Shiv Mani
AU - Carrillo Carrasco, Vanessa Polet
AU - Boeren, Sjef
AU - Monzer, Aline
AU - Koehorst, Jasper
AU - Kohchi, Takayuki
AU - Nishihama, Ryuichi
AU - Fendrych, Matyas
AU - Sprakel, Joris
AU - Friml, Jiří
AU - Weijers, Dolf
ID - 14826
IS - 1
JF - Cell
KW - General Biochemistry
KW - Genetics and Molecular Biology
SN - 0092-8674
TI - RAF-like protein kinases mediate a deeply conserved, rapid auxin response
VL - 187
ER -
TY - JOUR
AB - The phytohormone auxin and its directional transport through tissues play a fundamental role in development of higher plants. This polar auxin transport predominantly relies on PIN-FORMED (PIN) auxin exporters. Hence, PIN polarization is crucial for development, but its evolution during the rise of morphological complexity in land plants remains unclear. Here, we performed a cross-species investigation by observing the trafficking and localization of endogenous and exogenous PINs in two bryophytes, Physcomitrium patens and Marchantia polymorpha, and in the flowering plant Arabidopsis thaliana. We confirmed that the GFP fusion did not compromise the auxin export function of all examined PINs by using radioactive auxin export assay and by observing the phenotypic changes in transgenic bryophytes. Endogenous PINs polarize to filamentous apices, while exogenous Arabidopsis PINs distribute symmetrically on the membrane in both bryophytes. In Arabidopsis root epidermis, bryophytic PINs show no defined polarity. Pharmacological interference revealed a strong cytoskeleton dependence of bryophytic but not Arabidopsis PIN polarization. The divergence of PIN polarization and trafficking is also observed within the bryophyte clade and between tissues of individual species. These results collectively reveal a divergence of PIN trafficking and polarity mechanisms throughout land plant evolution and a co-evolution of PIN sequence-based and cell-based polarity mechanisms.
AU - Tang, Han
AU - Lu, KJ
AU - Zhang, Y
AU - Cheng, YL
AU - Tu, SL
AU - Friml, Jiří
ID - 14251
IS - 1
JF - Plant Communications
SN - 2590-3462
TI - Divergence of trafficking and polarization mechanisms for PIN auxin transporters during land plant evolution
VL - 5
ER -
TY - JOUR
AB - The GNOM (GN) Guanine nucleotide Exchange Factor for ARF small GTPases (ARF-GEF) is among the best studied trafficking regulators in plants, playing crucial and unique developmental roles in patterning and polarity. The current models place GN at the Golgi apparatus (GA), where it mediates secretion/recycling, and at the plasma membrane (PM) presumably contributing to clathrin-mediated endocytosis (CME). The mechanistic basis of the developmental function of GN, distinct from the other ARF-GEFs including its closest homologue GNOM-LIKE1 (GNL1), remains elusive. Insights from this study largely extend the current notions of GN function. We show that GN, but not GNL1, localizes to the cell periphery at long-lived structures distinct from clathrin-coated pits, while CME and secretion proceed normally in gn knockouts. The functional GN mutant variant GNfewerroots, absent from the GA, suggests that the cell periphery is the major site of GN action responsible for its developmental function. Following inhibition by Brefeldin A, GN, but not GNL1, relocates to the PM likely on exocytic vesicles, suggesting selective molecular associations en route to the cell periphery. A study of GN-GNL1 chimeric ARF-GEFs indicates that all GN domains contribute to the specific GN function in a partially redundant manner. Together, this study offers significant steps toward the elucidation of the mechanism underlying unique cellular and development functions of GNOM.
AU - Adamowski, Maciek
AU - Matijevic, Ivana
AU - Friml, Jiří
ID - 15033
JF - eLife
KW - General Immunology and Microbiology
KW - General Biochemistry
KW - Genetics and Molecular Biology
KW - General Medicine
KW - General Neuroscience
SN - 2050-084X
TI - Developmental patterning function of GNOM ARF-GEF mediated from the cell periphery
VL - 13
ER -
TY - JOUR
AB - Salicylic acid (SA) plays important roles in different aspects of plant development, including root growth, where auxin is also a major player by means of its asymmetric distribution. However, the mechanism underlying the effect of SA on the development of rice roots remains poorly understood. Here, we show that SA inhibits rice root growth by interfering with auxin transport associated with the OsPIN3t- and clathrin-mediated gene regulatory network (GRN). SA inhibits root growth as well as Brefeldin A-sensitive trafficking through a non-canonical SA signaling mechanism. Transcriptome analysis of rice seedlings treated with SA revealed that the OsPIN3t auxin transporter is at the center of a GRN involving the coat protein clathrin. The root growth and endocytic trafficking in both the pin3t and clathrin heavy chain mutants were SA insensitivity. SA inhibitory effect on the endocytosis of OsPIN3t was dependent on clathrin; however, the root growth and endocytic trafficking mediated by tyrphostin A23 (TyrA23) were independent of the pin3t mutant under SA treatment. These data reveal that SA affects rice root growth through the convergence of transcriptional and non-SA signaling mechanisms involving OsPIN3t-mediated auxin transport and clathrin-mediated trafficking as key components.
AU - Jiang, Lihui
AU - Yao, Baolin
AU - Zhang, Xiaoyan
AU - Wu, Lixia
AU - Fu, Qijing
AU - Zhao, Yiting
AU - Cao, Yuxin
AU - Zhu, Ruomeng
AU - Lu, Xinqi
AU - Huang, Wuying
AU - Zhao, Jianping
AU - Li, Kuixiu
AU - Zhao, Shuanglu
AU - Han, Li
AU - Zhou, Xuan
AU - Luo, Chongyu
AU - Zhu, Haiyan
AU - Yang, Jing
AU - Huang, Huichuan
AU - Zhu, Zhengge
AU - He, Xiahong
AU - Friml, Jiří
AU - Zhang, Zhongkai
AU - Liu, Changning
AU - Du, Yunlong
ID - 12878
IS - 1
JF - Plant Journal
SN - 0960-7412
TI - Salicylic acid inhibits rice endocytic protein trafficking mediated by OsPIN3t and clathrin to affect root growth
VL - 115
ER -
TY - JOUR
AB - The primary cell wall is a fundamental plant constituent that is flexible but sufficiently rigid to support the plant cell shape. Although many studies have demonstrated that reactive oxygen species (ROS) serve as important signaling messengers to modify the cell wall structure and affect cellular growth, the regulatory mechanism underlying the spatial-temporal regulation of ROS activity for cell wall maintenance remains largely unclear. Here, we demonstrate the role of the Arabidopsis (Arabidopsis thaliana) multicopper oxidase-like protein skewed 5 (SKU5) and its homolog SKU5-similar 1 (SKS1) in root cell wall formation through modulating ROS homeostasis. Loss of SKU5 and SKS1 function resulted in aberrant division planes, protruding cell walls, ectopic deposition of iron, and reduced nicotinamide adeninedinucleotide phosphate (NADPH) oxidase-dependent ROS overproduction in the root epidermis–cortex and cortex–endodermis junctions. A decrease in ROS level or inhibition of NADPH oxidase activity rescued the cell wall defects of sku5 sks1 double mutants. SKU5 and SKS1 proteins were activated by iron treatment, and iron over-accumulated in the walls between the root epidermis and cortex cell layers of sku5 sks1. The glycosylphosphatidylinositol-anchored motif was crucial for membrane association and functionality of SKU5 and SKS1. Overall, our results identified SKU5 and SKS1 as regulators of ROS at the cell surface for regulation of cell wall structure and root cell growth.
AU - Chen, C
AU - Zhang, Y
AU - Cai, J
AU - Qiu, Y
AU - Li, L
AU - Gao, C
AU - Gao, Y
AU - Ke, M
AU - Wu, S
AU - Wei, C
AU - Chen, J
AU - Xu, T
AU - Friml, Jiří
AU - Wang, J
AU - Li, R
AU - Chao, D
AU - Zhang, B
AU - Chen, X
AU - Gao, Z
ID - 13213
IS - 3
JF - Plant Physiology
SN - 0032-0889
TI - Multi-copper oxidases SKU5 and SKS1 coordinate cell wall formation using apoplastic redox-based reactions in roots
VL - 192
ER -
TY - JOUR
AB - Treating sick group members is a hallmark of collective disease defence in vertebrates and invertebrates alike. Despite substantial effects on pathogen fitness and epidemiology, it is still largely unknown how pathogens react to the selection pressure imposed by care intervention. Using social insects and pathogenic fungi, we here performed a serial passage experiment in the presence or absence of colony members, which provide social immunity by grooming off infectious spores from exposed individuals. We found specific effects on pathogen diversity, virulence and transmission. Under selection of social immunity, pathogens invested into higher spore production, but spores were less virulent. Notably, they also elicited a lower grooming response in colony members, compared with spores from the individual host selection lines. Chemical spore analysis suggested that the spores from social selection lines escaped the caregivers’ detection by containing lower levels of ergosterol, a key fungal membrane component. Experimental application of chemically pure ergosterol indeed induced sanitary grooming, supporting its role as a microbe-associated cue triggering host social immunity against fungal pathogens. By reducing this detection cue, pathogens were able to evade the otherwise very effective collective disease defences of their social hosts.
AU - Stock, Miriam
AU - Milutinovic, Barbara
AU - Hönigsberger, Michaela
AU - Grasse, Anna V
AU - Wiesenhofer, Florian
AU - Kampleitner, Niklas
AU - Narasimhan, Madhumitha
AU - Schmitt, Thomas
AU - Cremer, Sylvia
ID - 12543
JF - Nature Ecology and Evolution
TI - Pathogen evasion of social immunity
VL - 7
ER -
TY - JOUR
AB - To respond to auxin, the chief orchestrator of their multicellularity, plants evolved multiple receptor systems and signal transduction cascades. Despite decades of research, however, we are still lacking a satisfactory synthesis of various auxin signaling mechanisms. The chief discrepancy and historical controversy of the field is that of rapid and slow auxin effects on plant physiology and development. How is it possible that ions begin to trickle across the plasma membrane as soon as auxin enters the cell, even though the best-characterized transcriptional auxin pathway can take effect only after tens of minutes? Recently, unexpected progress has been made in understanding this and other unknowns of auxin signaling. We provide a perspective on these exciting developments and concepts whose general applicability might have ramifications beyond auxin signaling.
AU - Fiedler, Lukas
AU - Friml, Jiří
ID - 14313
IS - 10
JF - Current Opinion in Plant Biology
SN - 1369-5266
TI - Rapid auxin signaling: Unknowns old and new
VL - 75
ER -
TY - GEN
AB - Clathrin-mediated endocytosis (CME) is vital for the regulation of plant growth and development by controlling plasma membrane protein composition and cargo uptake. CME relies on the precise recruitment of regulators for vesicle maturation and release. Homologues of components of mammalian vesicle scission are strong candidates to be part of the scissin machinery in plants, but the precise roles of these proteins in this process is not fully understood. Here, we characterised the roles of Plant Dynamin-Related Proteins 2 (DRP2s) and SH3-domain containing protein 2 (SH3P2), the plant homologue to Dynamins’ recruiters, like Endophilin and Amphiphysin, in the CME by combining high-resolution imaging of endocytic events in vivo and characterisation of the purified proteins in vitro. Although DRP2s and SH3P2 arrive similarly late during CME and physically interact, genetic analysis of the Dsh3p1,2,3 triple-mutant and complementation assays with non-SH3P2-interacting DRP2 variants suggests that SH3P2 does not directly recruit DRP2s to the site of endocytosis. These observations imply that despite the presence of many well-conserved endocytic components, plants have acquired a distinct mechanism for CME. One Sentence Summary In contrast to predictions based on mammalian systems, plant Dynamin-related proteins 2 are recruited to the site of Clathrin-mediated endocytosis independently of BAR-SH3 proteins.
AU - Gnyliukh, Nataliia
AU - Johnson, Alexander J
AU - Nagel, Marie-Kristin
AU - Monzer, Aline
AU - Hlavata, Annamaria
AU - Isono, Erika
AU - Loose, Martin
AU - Friml, Jiří
ID - 14591
T2 - bioRxiv
TI - Role of dynamin-related proteins 2 and SH3P2 in clathrin-mediated endocytosis in plants
ER -
TY - JOUR
AB - Lateral roots are typically maintained at non-vertical angles with respect to gravity. These gravitropic setpoint angles are intriguing because their maintenance requires that roots are able to effect growth response both with and against the gravity vector, a phenomenon previously attributed to gravitropism acting against an antigravitropic offset mechanism. Here we show how the components mediating gravitropism in the vertical primary root—PINs and phosphatases acting upon them—are reconfigured in their regulation such that lateral root growth at a range of angles can be maintained. We show that the ability of Arabidopsis lateral roots to bend both downward and upward requires the generation of auxin asymmetries and is driven by angle-dependent variation in downward gravitropic auxin flux acting against angle-independent upward, antigravitropic flux. Further, we demonstrate a symmetry in auxin distribution in lateral roots at gravitropic setpoint angle that can be traced back to a net, balanced polarization of PIN3 and PIN7 auxin transporters in the columella. These auxin fluxes are shifted by altering PIN protein phosphoregulation in the columella, either by introducing PIN3 phosphovariant versions or via manipulation of levels of the phosphatase subunit PP2A/RCN1. Finally, we show that auxin, in addition to driving lateral root directional growth, acts within the lateral root columella to induce more vertical growth by increasing RCN1 levels, causing a downward shift in PIN3 localization, thereby diminishing the magnitude of the upward, antigravitropic auxin flux.
AU - Roychoudhry, S
AU - Sageman-Furnas, K
AU - Wolverton, C
AU - Grones, Peter
AU - Tan, Shutang
AU - Molnar, Gergely
AU - De Angelis, M
AU - Goodman, HL
AU - Capstaff, N
AU - JPB, Lloyd
AU - Mullen, J
AU - Hangarter, R
AU - Friml, Jiří
AU - Kepinski, S
ID - 14339
JF - Nature Plants
SN - 2055-0278
TI - Antigravitropic PIN polarization maintains non-vertical growth in lateral roots
VL - 9
ER -
TY - JOUR
AB - Auxin belongs among major phytohormones and governs multiple aspects of plant growth and development. The establishment of auxin concentration gradients, determines, among other processes, plant organ positioning and growth responses to environmental stimuli.
Herein we report the synthesis of new NBD- or DNS-labelled IAA derivatives and the elucidation of their biological activity, fluorescence properties and subcellular accumulation patterns in planta. These novel compounds did not show auxin-like activity, but instead antagonized physiological auxin effects. The DNS-labelled derivatives FL5 and FL6 showed strong anti-auxin activity in roots and hypocotyls, which also occurred at the level of gene transcription as confirmed by quantitative PCR analysis. The auxin antagonism of our derivatives was further demonstrated in vitro using an SPR-based binding assay. The NBD-labelled compound FL4 with the best fluorescence properties proved to be unsuitable to study auxin accumulation patterns in planta. On the other hand, the strongest anti-auxin activity possessing compounds FL5 and FL6 could be useful to study binding mechanisms to auxin receptors and for manipulations of auxin-regulated processes.
AU - Bieleszová, Kristýna
AU - Hladík, Pavel
AU - Kubala, Martin
AU - Napier, Richard
AU - Brunoni, Federica
AU - Gelová, Zuzana
AU - Fiedler, Lukas
AU - Kulich, Ivan
AU - Strnad, Miroslav
AU - Doležal, Karel
AU - Novák, Ondřej
AU - Friml, Jiří
AU - Žukauskaitė, Asta
ID - 14447
JF - Plant Growth Regulation
SN - 0167-6903
TI - New fluorescent auxin derivatives: anti-auxin activity and accumulation patterns in Arabidopsis thaliana
ER -
TY - JOUR
AB - Amid the delays due to the global pandemic, in early October 2022, the auxin community gathered in the idyllic peninsula of Cavtat, Croatia. More than 170 scientists from across the world converged to discuss the latest advancements in fundamental and applied research in the field. The topics, from signalling and transport to plant architecture and response to the environment, show how auxin research must bridge from the molecular realm to macroscopic developmental responses. This is mirrored in this collection of reviews, contributed by participants of the Auxin 2022 meeting.
AU - Del Bianco, Marta
AU - Friml, Jiří
AU - Strader, Lucia
AU - Kepinski, Stefan
ID - 14709
IS - 22
JF - Journal of Experimental Botany
SN - 0022-0957
TI - Auxin research: Creating tools for a greener future
VL - 74
ER -
TY - JOUR
AB - Soluble chaperones residing in the endoplasmic reticulum (ER) play vitally important roles in folding and quality control of newly synthesized proteins that transiently pass through the ER en route to their final destinations. These soluble residents of the ER are themselves endowed with an ER retrieval signal that enables the cell to bring the escaped residents back from the Golgi. Here, by using purified proteins, we showed that Nicotiana tabacum phytaspase, a plant aspartate-specific protease, introduces two breaks at the C-terminus of the N. tabacum ER resident calreticulin-3. These cleavages resulted in removal of either a dipeptide or a hexapeptide from the C-terminus of calreticulin-3 encompassing part or all of the ER retrieval signal. Consistently, expression of the calreticulin-3 derivative mimicking the phytaspase cleavage product in Nicotiana benthamiana cells demonstrated loss of the ER accumulation of the protein. Notably, upon its escape from the ER, calreticulin-3 was further processed by an unknown protease(s) to generate the free N-terminal (N) domain of calreticulin-3, which was ultimately secreted into the apoplast. Our study thus identified a specific proteolytic enzyme capable of precise detachment of the ER retrieval signal from a plant ER resident protein, with implications for the further fate of the escaped resident.
AU - Teplova, Anastasiia
AU - Pigidanov, Artemii A.
AU - Serebryakova, Marina V.
AU - Golyshev, Sergei A.
AU - Galiullina, Raisa A.
AU - Chichkova, Nina V.
AU - Vartapetian, Andrey B.
ID - 14776
IS - 22
JF - International Journal of Molecular Sciences
KW - Inorganic Chemistry
KW - Organic Chemistry
KW - Physical and Theoretical Chemistry
KW - Computer Science Applications
KW - Spectroscopy
KW - Molecular Biology
KW - General Medicine
KW - Catalysis
SN - 1422-0067
TI - Phytaspase Is capable of detaching the endoplasmic reticulum retrieval signal from tobacco calreticulin-3
VL - 24
ER -
TY - JOUR
AB - Auxin is the major plant hormone regulating growth and development (Friml, 2022). Forward genetic approaches in the model plant Arabidopsis thaliana have identified major components of auxin signalling and established the canonical mechanism mediating transcriptional and thus developmental reprogramming. In this textbook view, TRANSPORT INHIBITOR RESPONSE 1 (TIR1)/AUXIN-SIGNALING F-BOX (AFBs) are auxin receptors, which act as F-box subunits determining the substrate specificity of the Skp1-Cullin1-F box protein (SCF) type E3 ubiquitin ligase complex. Auxin acts as a “molecular glue” increasing the affinity between TIR1/AFBs and the Aux/IAA repressors. Subsequently, Aux/IAAs are ubiquitinated and degraded, thus releasing auxin transcription factors from their repression making them free to mediate transcription of auxin response genes (Yu et al., 2022). Nonetheless, accumulating evidence suggests existence of rapid, non-transcriptional responses downstream of TIR1/AFBs such as auxin-induced cytosolic calcium (Ca2+) transients, plasma membrane depolarization and apoplast alkalinisation, all converging on the process of root growth inhibition and root gravitropism (Li et al., 2022). Particularly, these rapid responses are mostly contributed by predominantly cytosolic AFB1, while the long-term growth responses are mediated by mainly nuclear TIR1 and AFB2-AFB5 (Li et al., 2021; Prigge et al., 2020; Serre et al., 2021). How AFB1 conducts auxin-triggered rapid responses and how it is different from TIR1 and AFB2-AFB5 remains elusive. Here, we compare the roles of TIR1 and AFB1 in transcriptional and rapid responses by modulating their subcellular localization in Arabidopsis and by testing their ability to mediate transcriptional responses when part of the minimal auxin circuit reconstituted in yeast.
AU - Chen, Huihuang
AU - Li, Lanxin
AU - Zou, Minxia
AU - Qi, Linlin
AU - Friml, Jiří
ID - 13212
IS - 7
JF - Molecular Plant
SN - 1752-9867
TI - Distinct functions of TIR1 and AFB1 receptors in auxin signalling.
VL - 16
ER -
TY - JOUR
AB - The 3′,5′-cyclic adenosine monophosphate (cAMP) is a versatile second messenger in many mammalian signaling pathways. However, its role in plants remains not well-recognized. Recent discovery of adenylate cyclase (AC) activity for transport inhibitor response 1/auxin-signaling F-box proteins (TIR1/AFB) auxin receptors and the demonstration of its importance for canonical auxin signaling put plant cAMP research back into spotlight. This insight briefly summarizes the well-established cAMP signaling pathways in mammalian cells and describes the turbulent and controversial history of plant cAMP research highlighting the major progress and the unresolved points. We also briefly review the current paradigm of auxin signaling to provide a background for the discussion on the AC activity of TIR1/AFB auxin receptors and its potential role in transcriptional auxin signaling as well as impact of these discoveries on plant cAMP research in general.
AU - Qi, Linlin
AU - Friml, Jiří
ID - 13266
IS - 2
JF - New Phytologist
SN - 0028-646X
TI - Tale of cAMP as a second messenger in auxin signaling and beyond
VL - 240
ER -
TY - JOUR
AB - The phytohormone auxin plays central roles in many growth and developmental processes in plants. Development of chemical tools targeting the auxin pathway is useful for both plant biology and agriculture. Here we reveal that naproxen, a synthetic compound with anti-inflammatory activity in humans, acts as an auxin transport inhibitor targeting PIN-FORMED (PIN) transporters in plants. Physiological experiments indicate that exogenous naproxen treatment affects pleiotropic auxin-regulated developmental processes. Additional cellular and biochemical evidence indicates that naproxen suppresses auxin transport, specifically PIN-mediated auxin efflux. Moreover, biochemical and structural analyses confirm that naproxen binds directly to PIN1 protein via the same binding cavity as the indole-3-acetic acid substrate. Thus, by combining cellular, biochemical, and structural approaches, this study clearly establishes that naproxen is a PIN inhibitor and elucidates the underlying mechanisms. Further use of this compound may advance our understanding of the molecular mechanisms of PIN-mediated auxin transport and expand our toolkit in auxin biology and agriculture.
AU - Xia, Jing
AU - Kong, Mengjuan
AU - Yang, Zhisen
AU - Sun, Lianghanxiao
AU - Peng, Yakun
AU - Mao, Yanbo
AU - Wei, Hong
AU - Ying, Wei
AU - Gao, Yongxiao
AU - Friml, Jiří
AU - Weng, Jianping
AU - Liu, Xin
AU - Sun, Linfeng
AU - Tan, Shutang
ID - 13209
IS - 6
JF - Plant Communications
TI - Chemical inhibition of Arabidopsis PIN-FORMED auxin transporters by the anti-inflammatory drug naproxen
VL - 4
ER -
TY - JOUR
AB - As a crucial nitrogen source, nitrate (NO3−) is a key nutrient for plants. Accordingly, root systems adapt to maximize NO3− availability, a developmental regulation also involving the phytohormone auxin. Nonetheless, the molecular mechanisms underlying this regulation remain poorly understood. Here, we identify low-nitrate-resistant mutant (lonr) in Arabidopsis (Arabidopsis thaliana), whose root growth fails to adapt to low-NO3− conditions. lonr2 is defective in the high-affinity NO3− transporter NRT2.1. lonr2 (nrt2.1) mutants exhibit defects in polar auxin transport, and their low-NO3−-induced root phenotype depends on the PIN7 auxin exporter activity. NRT2.1 directly associates with PIN7 and antagonizes PIN7-mediated auxin efflux depending on NO3− levels. These results reveal a mechanism by which NRT2.1 in response to NO3− limitation directly regulates auxin transport activity and, thus, root growth. This adaptive mechanism contributes to the root developmental plasticity to help plants cope with changes in NO3− availability.
AU - Wang, Yalu
AU - Yuan, Zhi
AU - Wang, Jinyi
AU - Xiao, Huixin
AU - Wan, Lu
AU - Li, Lanxin
AU - Guo, Yan
AU - Gong, Zhizhong
AU - Friml, Jiří
AU - Zhang, Jing
ID - 13201
IS - 25
JF - Proceedings of the National Academy of Sciences of the United States of America
SN - 0027-8424
TI - The nitrate transporter NRT2.1 directly antagonizes PIN7-mediated auxin transport for root growth adaptation
VL - 120
ER -
TY - THES
AU - Gnyliukh, Nataliia
ID - 14510
KW - Clathrin-Mediated Endocytosis
KW - vesicle scission
KW - Dynamin-Related Protein 2
KW - SH3P2
KW - TPLATE complex
KW - Total internal reflection fluorescence microscopy
KW - Arabidopsis thaliana
SN - 2663-337X
TI - Mechanism of clathrin-coated vesicle formation during endocytosis in plants
ER -
TY - JOUR
AB - Auxin has always been at the forefront of research in plant physiology and development. Since the earliest contemplations by Julius von Sachs and Charles Darwin, more than a century-long struggle has been waged to understand its function. This largely reflects the failures, successes, and inevitable progress in the entire field of plant signaling and development. Here I present 14 stations on our long and sometimes mystical journey to understand auxin. These highlights were selected to give a flavor of the field and to show the scope and limits of our current knowledge. A special focus is put on features that make auxin unique among phytohormones, such as its dynamic, directional transport network, which integrates external and internal signals, including self-organizing feedback. Accented are persistent mysteries and controversies. The unexpected discoveries related to rapid auxin responses and growth regulation recently disturbed our contentment regarding understanding of the auxin signaling mechanism. These new revelations, along with advances in technology, usher us into a new, exciting era in auxin research.
AU - Friml, Jiří
ID - 10016
IS - 5
JF - Cold Spring Harbor Perspectives in Biology
SN - 1943-0264
TI - Fourteen stations of auxin
VL - 14
ER -
TY - JOUR
AB - The synthetic strigolactone (SL) analog, rac-GR24, has been instrumental in studying the role of SLs as well as karrikins because it activates the receptors DWARF14 (D14) and KARRIKIN INSENSITIVE 2 (KAI2) of their signaling pathways, respectively. Treatment with rac-GR24 modifies the root architecture at different levels, such as decreasing the lateral root density (LRD), while promoting root hair elongation or flavonol accumulation. Previously, we have shown that the flavonol biosynthesis is transcriptionally activated in the root by rac-GR24 treatment, but, thus far, the molecular players involved in that response have remained unknown. To get an in-depth insight into the changes that occur after the compound is perceived by the roots, we compared the root transcriptomes of the wild type and the more axillary growth2 (max2) mutant, affected in both SL and karrikin signaling pathways, with and without rac-GR24 treatment. Quantitative reverse transcription (qRT)-PCR, reporter line analysis and mutant phenotyping indicated that the flavonol response and the root hair elongation are controlled by the ELONGATED HYPOCOTYL 5 (HY5) and MYB12 transcription factors, but HY5, in contrast to MYB12, affects the LRD as well. Furthermore, we identified the transcription factors TARGET OF MONOPTEROS 5 (TMO5) and TMO5 LIKE1 as negative and the Mediator complex as positive regulators of the rac-GR24 effect on LRD. Altogether, hereby, we get closer toward understanding the molecular mechanisms that underlay the rac-GR24 responses in the root.
AU - Struk, Sylwia
AU - Braem, Lukas
AU - Matthys, Cedrick
AU - Walton, Alan
AU - Vangheluwe, Nick
AU - Van Praet, Stan
AU - Jiang, Lingxiang
AU - Baster, Pawel
AU - De Cuyper, Carolien
AU - Boyer, Francois-Didier
AU - Stes, Elisabeth
AU - Beeckman, Tom
AU - Friml, Jiří
AU - Gevaert, Kris
AU - Goormachtig, Sofie
ID - 10583
IS - 1
JF - Plant & Cell Physiology
KW - flavonols
KW - MAX2
KW - rac-Gr24
KW - RNA-seq
KW - root development
KW - transcriptional regulation
SN - 0032-0781
TI - Transcriptional analysis in the Arabidopsis roots reveals new regulators that link rac-GR24 treatment with changes in flavonol accumulation, root hair elongation and lateral root density
VL - 63
ER -
TY - JOUR
AB - Much of what we know about the role of auxin in plant development derives from exogenous manipulations of auxin distribution and signaling, using inhibitors, auxins and auxin analogs. In this context, synthetic auxin analogs, such as 1-Naphtalene Acetic Acid (1-NAA), are often favored over the endogenous auxin indole-3-acetic acid (IAA), in part due to their higher stability. While such auxin analogs have proven to be instrumental to reveal the various faces of auxin, they display in some cases distinct bioactivities compared to IAA. Here, we focused on the effect of auxin analogs on the accumulation of PIN proteins in Brefeldin A-sensitive endosomal aggregations (BFA bodies), and the correlation with the ability to elicit Ca 2+ responses. For a set of commonly used auxin analogs, we evaluated if auxin-analog induced Ca 2+ signaling inhibits PIN accumulation. Not all auxin analogs elicited a Ca 2+ response, and their differential ability to elicit Ca 2+ responses correlated partially with their ability to inhibit BFA-body formation. However, in tir1/afb and cngc14, 1-NAA-induced Ca 2+ signaling was strongly impaired, yet 1-NAA still could inhibit PIN accumulation in BFA bodies. This demonstrates that TIR1/AFB-CNGC14-dependent Ca 2+ signaling does not inhibit BFA body formation in Arabidopsis roots.
AU - Wang, R
AU - Himschoot, E
AU - Grenzi, M
AU - Chen, J
AU - Safi, A
AU - Krebs, M
AU - Schumacher, K
AU - Nowack, MK
AU - Moeder, W
AU - Yoshioka, K
AU - Van Damme, D
AU - De Smet, I
AU - Geelen, D
AU - Beeckman, T
AU - Friml, Jiří
AU - Costa, A
AU - Vanneste, S
ID - 10717
IS - 8
JF - Journal of Experimental Botany
SN - 0022-0957
TI - Auxin analog-induced Ca2+ signaling is independent of inhibition of endosomal aggregation in Arabidopsis roots
VL - 73
ER -
TY - JOUR
AB - Auxin, one of the first identified and most widely studied phytohormones, has been and will remain a hot topic in plant biology. After more than a century of passionate exploration, the mysteries of its synthesis, transport, signaling, and metabolism have largely been unlocked. Due to the rapid development of new technologies, new methods, and new genetic materials, the study of auxin has entered the fast lane over the past 30 years. Here, we highlight advances in understanding auxin signaling, including auxin perception, rapid auxin responses, TRANSPORT INHIBITOR RESPONSE 1 and AUXIN SIGNALING F-boxes (TIR1/AFBs)-mediated transcriptional and non-transcriptional branches, and the epigenetic regulation of auxin signaling. We also focus on feedback inhibition mechanisms that prevent the over-amplification of auxin signals. In addition, we cover the TRANSMEMBRANE KINASEs (TMKs)-mediated non-canonical signaling, which converges with TIR1/AFBs-mediated transcriptional regulation to coordinate plant growth and development. The identification of additional auxin signaling components and their regulation will continue to open new avenues of research in this field, leading to an increasingly deeper, more comprehensive understanding of how auxin signals are interpreted at the cellular level to regulate plant growth and development.
AU - Yu, Z
AU - Zhang, F
AU - Friml, Jiří
AU - Ding, Z
ID - 10719
IS - 2
JF - Journal of Integrative Plant Biology
SN - 1672-9072
TI - Auxin signaling: Research advances over the past 30 years
VL - 64
ER -
TY - JOUR
AB - Among the most fascinated properties of the plant hormone auxin is its ability to promote formation of its own directional transport routes. These gradually narrowing auxin channels form from the auxin source toward the sink and involve coordinated, collective polarization of individual cells. Once established, the channels provide positional information, along which new vascular strands form, for example, during organogenesis, regeneration, or leave venation. The main prerequisite of this still mysterious auxin canalization mechanism is a feedback between auxin signaling and its directional transport. This is manifested by auxin-induced re-arrangements of polar, subcellular localization of PIN-FORMED (PIN) auxin exporters. Immanent open questions relate to how position of auxin source and sink as well as tissue context are sensed and translated into tissue polarization and how cells communicate to polarize coordinately. Recently, identification of the first molecular players opens new avenues into molecular studies of this intriguing example of self-organizing plant development.
AU - Hajny, Jakub
AU - Tan, Shutang
AU - Friml, Jiří
ID - 10768
IS - 2
JF - Current Opinion in Plant Biology
SN - 1369-5266
TI - Auxin canalization: From speculative models toward molecular players
VL - 65
ER -
TY - JOUR
AB - In eukaryotes, clathrin-coated vesicles (CCVs) facilitate the internalization of material from the cell surface as well as the movement of cargo in post-Golgi trafficking pathways. This diversity of functions is partially provided by multiple monomeric and multimeric clathrin adaptor complexes that provide compartment and cargo selectivity. The adaptor-protein assembly polypeptide-1 (AP-1) complex operates as part of the secretory pathway at the trans-Golgi network (TGN), while the AP-2 complex and the TPLATE complex jointly operate at the plasma membrane to execute clathrin-mediated endocytosis. Key to our further understanding of clathrin-mediated trafficking in plants will be the comprehensive identification and characterization of the network of evolutionarily conserved and plant-specific core and accessory machinery involved in the formation and targeting of CCVs. To facilitate these studies, we have analyzed the proteome of enriched TGN/early endosome-derived and endocytic CCVs isolated from dividing and expanding suspension-cultured Arabidopsis (Arabidopsis thaliana) cells. Tandem mass spectrometry analysis results were validated by differential chemical labeling experiments to identify proteins co-enriching with CCVs. Proteins enriched in CCVs included previously characterized CCV components and cargos such as the vacuolar sorting receptors in addition to conserved and plant-specific components whose function in clathrin-mediated trafficking has not been previously defined. Notably, in addition to AP-1 and AP-2, all subunits of the AP-4 complex, but not AP-3 or AP-5, were found to be in high abundance in the CCV proteome. The association of AP-4 with suspension-cultured Arabidopsis CCVs is further supported via additional biochemical data.
AU - Dahhan, DA
AU - Reynolds, GD
AU - Cárdenas, JJ
AU - Eeckhout, D
AU - Johnson, Alexander J
AU - Yperman, K
AU - Kaufmann, Walter
AU - Vang, N
AU - Yan, X
AU - Hwang, I
AU - Heese, A
AU - De Jaeger, G
AU - Friml, Jiří
AU - Van Damme, D
AU - Pan, J
AU - Bednarek, SY
ID - 10841
IS - 6
JF - Plant Cell
SN - 1040-4651
TI - Proteomic characterization of isolated Arabidopsis clathrin-coated vesicles reveals evolutionarily conserved and plant-specific components
VL - 34
ER -
TY - JOUR
AB - Despite the growing interest in using chemical genetics in plant research, small molecule target identification remains a major challenge. The cellular thermal shift assay coupled with high-resolution mass spectrometry (CETSA MS) that monitors changes in the thermal stability of proteins caused by their interactions with small molecules, other proteins, or posttranslational modifications, allows the discovery of drug targets or the study of protein–metabolite and protein–protein interactions mainly in mammalian cells. To showcase the applicability of this method in plants, we applied CETSA MS to intact Arabidopsis thaliana cells and identified the thermal proteome of the plant-specific glycogen synthase kinase 3 (GSK3) inhibitor, bikinin. A comparison between the thermal and the phosphoproteomes of bikinin revealed the auxin efflux carrier PIN-FORMED1 (PIN1) as a substrate of the Arabidopsis GSK3s that negatively regulate the brassinosteroid signaling. We established that PIN1 phosphorylation by the GSK3s is essential for maintaining its intracellular polarity that is required for auxin-mediated regulation of vascular patterning in the leaf, thus revealing cross-talk between brassinosteroid and auxin signaling.
AU - Lu, Qing
AU - Zhang, Yonghong
AU - Hellner, Joakim
AU - Giannini, Caterina
AU - Xu, Xiangyu
AU - Pauwels, Jarne
AU - Ma, Qian
AU - Dejonghe, Wim
AU - Han, Huibin
AU - Van De Cotte, Brigitte
AU - Impens, Francis
AU - Gevaert, Kris
AU - De Smet, Ive
AU - Friml, Jiří
AU - Molina, Daniel Martinez
AU - Russinova, Eugenia
ID - 10888
IS - 11
JF - Proceedings of the National Academy of Sciences of the United States of America
TI - Proteome-wide cellular thermal shift assay reveals unexpected cross-talk between brassinosteroid and auxin signaling
VL - 119
ER -
TY - JOUR
AB - Calcium-dependent protein kinases (CPK) are key components of a wide array of signaling pathways, translating stress and nutrient signaling into the modulation of cellular processes such as ion transport and transcription. However, not much is known about CPKs in endomembrane trafficking. Here, we screened for CPKs that impact on root growth and gravitropism, by overexpressing constitutively active forms of CPKs under the control of an inducible promoter in Arabidopsis thaliana. We found that inducible overexpression of an constitutive active CPK30 (CA-CPK30) resulted in a loss of root gravitropism and ectopic auxin accumulation in the root tip. Immunolocalization revealed that CA-CPK30 roots have reduced PIN protein levels, PIN1 polarity defects and impaired Brefeldin A (BFA)-sensitive trafficking. Moreover, FM4-64 uptake was reduced, indicative of a defect in endocytosis. The effects on BFA-sensitive trafficking were not specific to PINs, as BFA could not induce aggregation of ARF1- and CHC-labeled endosomes in CA-CPK30. Interestingly, the interference with BFA-body formation, could be reverted by increasing the extracellular pH, indicating a pH-dependence of this CA-CPK30 effect. Altogether, our data reveal an important role for CPK30 in root growth regulation and endomembrane trafficking in Arabidopsis thaliana.
AU - Wang, Ren
AU - Himschoot, Ellie
AU - Chen, Jian
AU - Boudsocq, Marie
AU - Geelen, Danny
AU - Friml, Jiří
AU - Beeckman, Tom
AU - Vanneste, Steffen
ID - 11589
JF - Frontiers in Plant Science
TI - Constitutive active CPK30 interferes with root growth and endomembrane trafficking in Arabidopsis thaliana
VL - 13
ER -
TY - JOUR
AB - Plant cell growth responds rapidly to various stimuli, adapting architecture to environmental changes. Two major endogenous signals regulating growth are the phytohormone auxin and the secreted peptides rapid alkalinization factors (RALFs). Both trigger very rapid cellular responses and also exert long-term effects [Du et al., Annu. Rev. Plant Biol. 71, 379–402 (2020); Blackburn et al., Plant Physiol. 182, 1657–1666 (2020)]. However, the way, in which these distinct signaling pathways converge to regulate growth, remains unknown. Here, using vertical confocal microscopy combined with a microfluidic chip, we addressed the mechanism of RALF action on growth. We observed correlation between RALF1-induced rapid Arabidopsis thaliana root growth inhibition and apoplast alkalinization during the initial phase of the response, and revealed that RALF1 reversibly inhibits primary root growth through apoplast alkalinization faster than within 1 min. This rapid apoplast alkalinization was the result of RALF1-induced net H+ influx and was mediated by the receptor FERONIA (FER). Furthermore, we investigated the cross-talk between RALF1 and the auxin signaling pathways during root growth regulation. The results showed that RALF-FER signaling triggered auxin signaling with a delay of approximately 1 h by up-regulating auxin biosynthesis, thus contributing to sustained RALF1-induced growth inhibition. This biphasic RALF1 action on growth allows plants to respond rapidly to environmental stimuli and also reprogram growth and development in the long term.
AU - Li, Lanxin
AU - Chen, Huihuang
AU - Alotaibi, Saqer S.
AU - Pěnčík, Aleš
AU - Adamowski, Maciek
AU - Novák, Ondřej
AU - Friml, Jiří
ID - 11723
IS - 31
JF - Proceedings of the National Academy of Sciences
KW - Multidisciplinary
SN - 0027-8424
TI - RALF1 peptide triggers biphasic root growth inhibition upstream of auxin biosynthesis
VL - 119
ER -
TY - JOUR
AB - Strigolactones (SLs) are a class of phytohormones that regulate plant shoot branching and adventitious root development. However, little is known regarding the role of SLs in controlling the behavior of the smallest unit of the organism, the single cell. Here, taking advantage of a classic single-cell model offered by the cotton (Gossypium hirsutum) fiber cell, we show that SLs, whose biosynthesis is fine-tuned by gibberellins (GAs), positively regulate cell elongation and cell wall thickness by promoting the biosynthesis of very-long-chain fatty acids (VLCFAs) and cellulose, respectively. Furthermore, we identified two layers of transcription factors (TFs) involved in the hierarchical regulation of this GA-SL crosstalk. The top-layer TF GROWTH-REGULATING FACTOR 4 (GhGRF4) directly activates expression of the SL biosynthetic gene DWARF27 (D27) to increase SL accumulation in fiber cells and GAs induce GhGRF4 expression. SLs induce the expression of four second-layer TF genes (GhNAC100-2, GhBLH51, GhGT2, and GhB9SHZ1), which transmit SL signals downstream to two ketoacyl-CoA synthase genes (KCS) and three cellulose synthase (CesA) genes by directly activating their transcription. Finally, the KCS and CesA enzymes catalyze the biosynthesis of very long chain fatty acids and cellulose, respectively, to regulate development of high-grade cotton fibers. In addition to providing a theoretical basis for cotton fiber improvement, our results shed light on SL signaling in plant development at the single-cell level.
AU - Tian, Z
AU - Zhang, Yuzhou
AU - Zhu, L
AU - Jiang, B
AU - Wang, H
AU - Gao, R
AU - Friml, Jiří
AU - Xiao, G
ID - 12053
IS - 12
JF - The Plant Cell
SN - 1040-4651
TI - Strigolactones act downstream of gibberellins to regulate fiber cell elongation and cell wall thickness in cotton (Gossypium hirsutum)
VL - 34
ER -
TY - JOUR
AB - Directionality in the intercellular transport of the plant hormone auxin is determined by polar plasma membrane localization of PIN-FORMED (PIN) auxin transport proteins. However, apart from PIN phosphorylation at conserved motifs, no further determinants explicitly controlling polar PIN sorting decisions have been identified. Here we present Arabidopsis WAVY GROWTH 3 (WAV3) and closely related RING-finger E3 ubiquitin ligases, whose loss-of-function mutants show a striking apical-to-basal polarity switch in PIN2 localization in root meristem cells. WAV3 E3 ligases function as essential determinants for PIN polarity, acting independently from PINOID/WAG-dependent PIN phosphorylation. They antagonize ectopic deposition of de novo synthesized PIN proteins already immediately following completion of cell division, presumably via preventing PIN sorting into basal, ARF GEF-mediated trafficking. Our findings reveal an involvement of E3 ligases in the selective targeting of apically localized PINs in higher plants.
AU - Konstantinova, N
AU - Hörmayer, Lukas
AU - Glanc, Matous
AU - Keshkeih, R
AU - Tan, Shutang
AU - Di Donato, M
AU - Retzer, K
AU - Moulinier-Anzola, J
AU - Schwihla, M
AU - Korbei, B
AU - Geisler, M
AU - Friml, Jiří
AU - Luschnig, C
ID - 12052
JF - Nature Communications
SN - 2041-1723
TI - WAVY GROWTH Arabidopsis E3 ubiquitin ligases affect apical PIN sorting decisions
VL - 13
ER -
TY - JOUR
AB - Polar auxin transport is unique to plants and coordinates their growth and development1,2. The PIN-FORMED (PIN) auxin transporters exhibit highly asymmetrical localizations at the plasma membrane and drive polar auxin transport3,4; however, their structures and transport mechanisms remain largely unknown. Here, we report three inward-facing conformation structures of Arabidopsis thaliana PIN1: the apo state, bound to the natural auxin indole-3-acetic acid (IAA), and in complex with the polar auxin transport inhibitor N-1-naphthylphthalamic acid (NPA). The transmembrane domain of PIN1 shares a conserved NhaA fold5. In the substrate-bound structure, IAA is coordinated by both hydrophobic stacking and hydrogen bonding. NPA competes with IAA for the same site at the intracellular pocket, but with a much higher affinity. These findings inform our understanding of the substrate recognition and transport mechanisms of PINs and set up a framework for future research on directional auxin transport, one of the most crucial processes underlying plant development.
AU - Yang, Z
AU - Xia, J
AU - Hong, J
AU - Zhang, C
AU - Wei, H
AU - Ying, W
AU - Sun, C
AU - Sun, L
AU - Mao, Y
AU - Gao, Y
AU - Tan, S
AU - Friml, Jiří
AU - Li, D
AU - Liu, X
AU - Sun, L
ID - 12054
IS - 7927
JF - Nature
SN - 0028-0836
TI - Structural insights into auxin recognition and efflux by Arabidopsis PIN1
VL - 609
ER -
TY - JOUR
AB - Autophagosomes are double-membraned vesicles that traffic harmful or unwanted cellular macromolecules to the vacuole for recycling. Although autophagosome biogenesis has been extensively studied, autophagosome maturation, i.e., delivery and fusion with the vacuole, remains largely unknown in plants. Here, we have identified an autophagy adaptor, CFS1, that directly interacts with the autophagosome marker ATG8 and localizes on both membranes of the autophagosome. Autophagosomes form normally in Arabidopsis thaliana cfs1 mutants, but their delivery to the vacuole is disrupted. CFS1’s function is evolutionarily conserved in plants, as it also localizes to the autophagosomes and plays a role in autophagic flux in the liverwort Marchantia polymorpha. CFS1 regulates autophagic flux by bridging autophagosomes with the multivesicular body-localized ESCRT-I component VPS23A, leading to the formation of amphisomes. Similar to CFS1-ATG8 interaction, disrupting the CFS1-VPS23A interaction blocks autophagic flux and renders plants sensitive to nitrogen starvation. Altogether, our results reveal a conserved vacuolar sorting hub that regulates autophagic flux in plants.
AU - Zhao, Jierui
AU - Bui, Mai Thu
AU - Ma, Juncai
AU - Künzl, Fabian
AU - Picchianti, Lorenzo
AU - De La Concepcion, Juan Carlos
AU - Chen, Yixuan
AU - Petsangouraki, Sofia
AU - Mohseni, Azadeh
AU - García-Leon, Marta
AU - Gomez, Marta Salas
AU - Giannini, Caterina
AU - Gwennogan, Dubois
AU - Kobylinska, Roksolana
AU - Clavel, Marion
AU - Schellmann, Swen
AU - Jaillais, Yvon
AU - Friml, Jiří
AU - Kang, Byung-Ho
AU - Dagdas, Yasin
ID - 12121
IS - 12
JF - Journal of Cell Biology
KW - Cell Biology
SN - 0021-9525
TI - Plant autophagosomes mature into amphisomes prior to their delivery to the central vacuole
VL - 221
ER -
TY - JOUR
AB - Germline determination is essential for species survival and evolution in multicellular organisms. In most flowering plants, formation of the female germline is initiated with specification of one megaspore mother cell (MMC) in each ovule; however, the molecular mechanism underlying this key event remains unclear. Here we report that spatially restricted auxin signaling promotes MMC fate in Arabidopsis. Our results show that the microRNA160 (miR160) targeted gene ARF17 (AUXIN RESPONSE FACTOR17) is required for promoting MMC specification by genetically interacting with the SPL/NZZ (SPOROCYTELESS/NOZZLE) gene. Alterations of auxin signaling cause formation of supernumerary MMCs in an ARF17- and SPL/NZZ-dependent manner. Furthermore, miR160 and ARF17 are indispensable for attaining a normal auxin maximum at the ovule apex via modulating the expression domain of PIN1 (PIN-FORMED1) auxin transporter. Our findings elucidate the mechanism by which auxin signaling promotes the acquisition of female germline cell fate in plants.
AU - Huang, Jian
AU - Zhao, Lei
AU - Malik, Shikha
AU - Gentile, Benjamin R.
AU - Xiong, Va
AU - Arazi, Tzahi
AU - Owen, Heather A.
AU - Friml, Jiří
AU - Zhao, Dazhong
ID - 12130
JF - Nature Communications
KW - General Physics and Astronomy
KW - General Biochemistry
KW - Genetics and Molecular Biology
KW - General Chemistry
KW - Multidisciplinary
SN - 2041-1723
TI - Specification of female germline by microRNA orchestrated auxin signaling in Arabidopsis
VL - 13
ER -
TY - JOUR
AB - Biological systems are the sum of their dynamic three-dimensional (3D) parts. Therefore, it is critical to study biological structures in 3D and at high resolution to gain insights into their physiological functions. Electron microscopy of metal replicas of unroofed cells and isolated organelles has been a key technique to visualize intracellular structures at nanometer resolution. However, many of these methods require specialized equipment and personnel to complete them. Here, we present novel accessible methods to analyze biological structures in unroofed cells and biochemically isolated organelles in 3D and at nanometer resolution, focusing on Arabidopsis clathrin-coated vesicles (CCVs). While CCVs are essential trafficking organelles, their detailed structural information is lacking due to their poor preservation when observed via classical electron microscopy protocols experiments. First, we establish a method to visualize CCVs in unroofed cells using scanning transmission electron microscopy tomography, providing sufficient resolution to define the clathrin coat arrangements. Critically, the samples are prepared directly on electron microscopy grids, removing the requirement to use extremely corrosive acids, thereby enabling the use of this method in any electron microscopy lab. Secondly, we demonstrate that this standardized sample preparation allows the direct comparison of isolated CCV samples with those visualized in cells. Finally, to facilitate the high-throughput and robust screening of metal replicated samples, we provide a deep learning analysis method to screen the “pseudo 3D” morphologies of CCVs imaged with 2D modalities. Collectively, our work establishes accessible ways to examine the 3D structure of biological samples and provide novel insights into the structure of plant CCVs.
AU - Johnson, Alexander J
AU - Kaufmann, Walter
AU - Sommer, Christoph M
AU - Costanzo, Tommaso
AU - Dahhan, Dana A.
AU - Bednarek, Sebastian Y.
AU - Friml, Jiří
ID - 12239
IS - 10
JF - Molecular Plant
KW - Plant Science
KW - Molecular Biology
SN - 1674-2052
TI - Three-dimensional visualization of planta clathrin-coated vesicles at ultrastructural resolution
VL - 15
ER -
TY - JOUR
AB - Much of plant development depends on cell-to-cell redistribution of the plant hormone auxin, which is facilitated by the plasma membrane (PM) localized PIN FORMED (PIN) proteins. Auxin export activity, developmental roles, subcellular trafficking, and polarity of PINs have been well studied, but their structure remains elusive besides a rough outline that they contain two groups of 5 alpha-helices connected by a large hydrophilic loop (HL). Here, we focus on the PIN1 HL as we could produce it in sufficient quantities for biochemical investigations to provide insights into its secondary structure. Circular dichroism (CD) studies revealed its nature as an intrinsically disordered protein (IDP), manifested by the increase of structure content upon thermal melting. Consistent with IDPs serving as interaction platforms, PIN1 loops homodimerize. PIN1 HL cytoplasmic overexpression in Arabidopsis disrupts early endocytic trafficking of PIN1 and PIN2 and causes defects in the cotyledon vasculature formation. In summary, we demonstrate that PIN1 HL has an intrinsically disordered nature, which must be considered to gain further structural insights. Some secondary structures may form transiently during pairing with known and yet-to-be-discovered interactors.
AU - Bilanovičová, V
AU - Rýdza, N
AU - Koczka, L
AU - Hess, M
AU - Feraru, E
AU - Friml, Jiří
AU - Nodzyński, T
ID - 11489
IS - 11
JF - International Journal of Molecular Sciences
SN - 1422-0067
TI - The hydrophilic loop of Arabidopsis PIN1 auxin efflux carrier harbors hallmarks of an intrinsically disordered protein
VL - 23
ER -
TY - JOUR
AB - The phytohormone auxin is the major coordinative signal in plant development1, mediating transcriptional reprogramming by a well-established canonical signalling pathway. TRANSPORT INHIBITOR RESPONSE 1 (TIR1)/AUXIN-SIGNALING F-BOX (AFB) auxin receptors are F-box subunits of ubiquitin ligase complexes. In response to auxin, they associate with Aux/IAA transcriptional repressors and target them for degradation via ubiquitination2,3. Here we identify adenylate cyclase (AC) activity as an additional function of TIR1/AFB receptors across land plants. Auxin, together with Aux/IAAs, stimulates cAMP production. Three separate mutations in the AC motif of the TIR1 C-terminal region, all of which abolish the AC activity, each render TIR1 ineffective in mediating gravitropism and sustained auxin-induced root growth inhibition, and also affect auxin-induced transcriptional regulation. These results highlight the importance of TIR1/AFB AC activity in canonical auxin signalling. They also identify a unique phytohormone receptor cassette combining F-box and AC motifs, and the role of cAMP as a second messenger in plants.
AU - Qi, Linlin
AU - Kwiatkowski, Mateusz
AU - Chen, Huihuang
AU - Hörmayer, Lukas
AU - Sinclair, Scott A
AU - Zou, Minxia
AU - del Genio, Charo I.
AU - Kubeš, Martin F.
AU - Napier, Richard
AU - Jaworski, Krzysztof
AU - Friml, Jiří
ID - 12144
IS - 7934
JF - Nature
SN - 0028-0836
TI - Adenylate cyclase activity of TIR1/AFB auxin receptors in plants
VL - 611
ER -
TY - JOUR
AB - Plant root architecture flexibly adapts to changing nitrate (NO3−) availability in the soil; however, the underlying molecular mechanism of this adaptive development remains under-studied. To explore the regulation of NO3−-mediated root growth, we screened for low-nitrate-resistant mutant (lonr) and identified mutants that were defective in the NAC transcription factor NAC075 (lonr1) as being less sensitive to low NO3− in terms of primary root growth. We show that NAC075 is a mobile transcription factor relocating from the root stele tissues to the endodermis based on NO3− availability. Under low-NO3− availability, the kinase CBL-interacting protein kinase 1 (CIPK1) is activated, and it phosphorylates NAC075, restricting its movement from the stele, which leads to the transcriptional regulation of downstream target WRKY53, consequently leading to adapted root architecture. Our work thus identifies an adaptive mechanism involving translocation of transcription factor based on nutrient availability and leading to cell-specific reprogramming of plant root growth.
AU - Xiao, Huixin
AU - Hu, Yumei
AU - Wang, Yaping
AU - Cheng, Jinkui
AU - Wang, Jinyi
AU - Chen, Guojingwei
AU - Li, Qian
AU - Wang, Shuwei
AU - Wang, Yalu
AU - Wang, Shao-Shuai
AU - Wang, Yi
AU - Xuan, Wei
AU - Li, Zhen
AU - Guo, Yan
AU - Gong, Zhizhong
AU - Friml, Jiří
AU - Zhang, Jing
ID - 12120
IS - 23
JF - Developmental Cell
KW - Developmental Biology
KW - Cell Biology
KW - General Biochemistry
KW - Genetics and Molecular Biology
KW - Molecular Biology
SN - 1534-5807
TI - Nitrate availability controls translocation of the transcription factor NAC075 for cell-type-specific reprogramming of root growth
VL - 57
ER -
TY - JOUR
AB - The phytohormone auxin triggers transcriptional reprogramming through a well-characterized perception machinery in the nucleus. By contrast, mechanisms that underlie fast effects of auxin, such as the regulation of ion fluxes, rapid phosphorylation of proteins or auxin feedback on its transport, remain unclear1,2,3. Whether auxin-binding protein 1 (ABP1) is an auxin receptor has been a source of debate for decades1,4. Here we show that a fraction of Arabidopsis thaliana ABP1 is secreted and binds auxin specifically at an acidic pH that is typical of the apoplast. ABP1 and its plasma-membrane-localized partner, transmembrane kinase 1 (TMK1), are required for the auxin-induced ultrafast global phospho-response and for downstream processes that include the activation of H+-ATPase and accelerated cytoplasmic streaming. abp1 and tmk mutants cannot establish auxin-transporting channels and show defective auxin-induced vasculature formation and regeneration. An ABP1(M2X) variant that lacks the capacity to bind auxin is unable to complement these defects in abp1 mutants. These data indicate that ABP1 is the auxin receptor for TMK1-based cell-surface signalling, which mediates the global phospho-response and auxin canalization.
AU - Friml, Jiří
AU - Gallei, Michelle C
AU - Gelová, Zuzana
AU - Johnson, Alexander J
AU - Mazur, Ewa
AU - Monzer, Aline
AU - Rodriguez Solovey, Lesia
AU - Roosjen, Mark
AU - Verstraeten, Inge
AU - Živanović, Branka D.
AU - Zou, Minxia
AU - Fiedler, Lukas
AU - Giannini, Caterina
AU - Grones, Peter
AU - Hrtyan, Mónika
AU - Kaufmann, Walter
AU - Kuhn, Andre
AU - Narasimhan, Madhumitha
AU - Randuch, Marek
AU - Rýdza, Nikola
AU - Takahashi, Koji
AU - Tan, Shutang
AU - Teplova, Anastasiia
AU - Kinoshita, Toshinori
AU - Weijers, Dolf
AU - Rakusová, Hana
ID - 12291
IS - 7927
JF - Nature
SN - 0028-0836
TI - ABP1–TMK auxin perception for global phosphorylation and auxin canalization
VL - 609
ER -
TY - THES
AB - Plant growth and development is well known to be both, flexible and dynamic. The high capacity for post-embryonic organ formation and tissue regeneration requires tightly regulated intercellular communication and coordinated tissue polarization. One of the most important drivers for patterning and polarity in plant development is the phytohormone auxin. Auxin has the unique characteristic to establish polarized channels for its own active directional cell to cell transport. This fascinating phenomenon is called auxin canalization. Those auxin transport channels are characterized by the expression and polar, subcellular localization of PIN auxin efflux carriers. PIN proteins have the ability to dynamically change their localization and auxin itself can affect this by interfering with trafficking. Most of the underlying molecular mechanisms of canalization still remain enigmatic. What is known so far is that canonical auxin signaling is indispensable but also other non-canonical signaling components are thought to play a role. In order to shed light into the mysteries auf auxin canalization this study revisits the branches of auxin signaling in detail. Further a new auxin analogue, PISA, is developed which triggers auxin-like responses but does not directly activate canonical transcriptional auxin signaling. We revisit the direct auxin effect on PIN trafficking where we found that, contradictory to previous observations, auxin is very specifically promoting endocytosis of PIN2 but has no overall effect on endocytosis. Further, we evaluate which cellular processes related to PIN subcellular dynamics are involved in the establishment of auxin conducting channels and the formation of vascular tissue. We are re-evaluating the function of AUXIN BINDING PROTEIN 1 (ABP1) and provide a comprehensive picture about its developmental phneotypes and involvement in auxin signaling and canalization. Lastly, we are focusing on the crosstalk between the hormone strigolactone (SL) and auxin and found that SL is interfering with essentially all processes involved in auxin canalization in a non-transcriptional manner. Lastly we identify a new way of SL perception and signaling which is emanating from mitochondria, is independent of canonical SL signaling and is modulating primary root growth.
AU - Gallei, Michelle C
ID - 11626
SN - 2663-337X
TI - Auxin and strigolactone non-canonical signaling regulating development in Arabidopsis thaliana
ER -
TY - JOUR
AB - The phytohormone auxin is the major growth regulator governing tropic responses including gravitropism. Auxin build-up at the lower side of stimulated shoots promotes cell expansion, whereas in roots it inhibits growth, leading to upward shoot bending and downward root bending, respectively. Yet it remains an enigma how the same signal can trigger such opposite cellular responses. In this review, we discuss several recent unexpected insights into the mechanisms underlying auxin regulation of growth, challenging several existing models. We focus on the divergent mechanisms of apoplastic pH regulation in shoots and roots revisiting the classical Acid Growth Theory and discuss coordinated involvement of multiple auxin signaling pathways. From this emerges a more comprehensive, updated picture how auxin regulates growth.
AU - Li, Lanxin
AU - Gallei, Michelle C
AU - Friml, Jiří
ID - 10411
IS - 5
JF - Trends in Plant Science
SN - 1360-1385
TI - Bending to auxin: Fast acid growth for tropisms
VL - 27
ER -
TY - JOUR
AB - Ustilago maydis is a biotrophic phytopathogenic fungus that causes corn smut disease. As a well-established model system, U. maydis is genetically fully accessible with large omics datasets available and subject to various biological questions ranging from DNA-repair, RNA-transport, and protein secretion to disease biology. For many genetic approaches, tight control of transgene regulation is important. Here we established an optimised version of the Tetracycline-ON (TetON) system for U. maydis. We demonstrate the Tetracycline concentration-dependent expression of fluorescent protein transgenes and the system’s suitability for the induced expression of the toxic protein BCL2 Associated X-1 (Bax1). The Golden Gate compatible vector system contains a native minimal promoter from the mating factor a-1 encoding gene, mfa with ten copies of the tet-regulated operator (tetO) and a codon optimised Tet-repressor (tetR*) which is translationally fused to the native transcriptional corepressor Mql1 (UMAG_05501). The metabolism-independent transcriptional regulator system is functional both, in liquid culture as well as on solid media in the presence of the inducer and can become a useful tool for toxin-antitoxin studies, identification of antifungal proteins, and to study functions of toxic gene products in Ustilago maydis.
AU - Ingole, Kishor D.
AU - Nagarajan, Nithya
AU - Uhse, Simon
AU - Giannini, Caterina
AU - Djamei, Armin
ID - 13240
JF - Frontiers in Fungal Biology
TI - Tetracycline-controlled (TetON) gene expression system for the smut fungus Ustilago maydis
VL - 3
ER -
TY - CHAP
AB - Tropisms are among the most important growth responses for plant adaptation to the surrounding environment. One of the most common tropisms is root gravitropism. Root gravitropism enables the plant to anchor securely to the soil enabling the absorption of water and nutrients. Most of the knowledge related to the plant gravitropism has been acquired from the flowering plants, due to limited research in non-seed plants. Limited research on non-seed plants is due in large part to the lack of standard research methods. Here, we describe the experimental methods to evaluate gravitropism in representative non-seed plant species, including the non-vascular plant moss Physcomitrium patens, the early diverging extant vascular plant lycophyte Selaginella moellendorffii and fern Ceratopteris richardii. In addition, we introduce the methods used for statistical analysis of the root gravitropism in non-seed plant species.
AU - Zhang, Yuzhou
AU - Li, Lanxin
AU - Friml, Jiří
ED - Blancaflor, Elison B
ID - 10267
SN - 978-1-0716-1676-5
T2 - Plant Gravitropism
TI - Evaluation of gravitropism in non-seed plants
VL - 2368
ER -
TY - CHAP
AB - The analysis of dynamic cellular processes such as plant cytokinesis stands and falls with live-cell time-lapse confocal imaging. Conventional approaches to time-lapse imaging of cell division in Arabidopsis root tips are tedious and have low throughput. Here, we describe a protocol for long-term time-lapse simultaneous imaging of multiple root tips on a vertical-stage confocal microscope with automated root tracking. We also provide modifications of the basic protocol to implement this imaging method in the analysis of genetic, pharmacological or laser ablation wounding-mediated experimental manipulations. Our method dramatically improves the efficiency of cell division time-lapse imaging by increasing the throughput, while reducing the person-hour requirements of such experiments.
AU - Hörmayer, Lukas
AU - Friml, Jiří
AU - Glanc, Matous
ID - 10268
SN - 1064-3745
T2 - Plant Cell Division
TI - Automated time-lapse imaging and manipulation of cell divisions in Arabidopsis roots by vertical-stage confocal microscopy
VL - 2382
ER -
TY - JOUR
AB - Cell and tissue polarization is fundamental for plant growth and morphogenesis. The polar, cellular localization of Arabidopsis PIN‐FORMED (PIN) proteins is crucial for their function in directional auxin transport. The clustering of PIN polar cargoes within the plasma membrane has been proposed to be important for the maintenance of their polar distribution. However, the more detailed features of PIN clusters and the cellular requirements of cargo clustering remain unclear.
Here, we characterized PIN clusters in detail by means of multiple advanced microscopy and quantification methods, such as 3D quantitative imaging or freeze‐fracture replica labeling. The size and aggregation types of PIN clusters were determined by electron microscopy at the nanometer level at different polar domains and at different developmental stages, revealing a strong preference for clustering at the polar domains.
Pharmacological and genetic studies revealed that PIN clusters depend on phosphoinositol pathways, cytoskeletal structures and specific cell‐wall components as well as connections between the cell wall and the plasma membrane.
This study identifies the role of different cellular processes and structures in polar cargo clustering and provides initial mechanistic insight into the maintenance of polarity in plants and other systems.
AU - Li, Hongjiang
AU - von Wangenheim, Daniel
AU - Zhang, Xixi
AU - Tan, Shutang
AU - Darwish-Miranda, Nasser
AU - Naramoto, Satoshi
AU - Wabnik, Krzysztof T
AU - de Rycke, Riet
AU - Kaufmann, Walter
AU - Gütl, Daniel J
AU - Tejos, Ricardo
AU - Grones, Peter
AU - Ke, Meiyu
AU - Chen, Xu
AU - Dettmer, Jan
AU - Friml, Jiří
ID - 8582
IS - 1
JF - New Phytologist
SN - 0028646X
TI - Cellular requirements for PIN polar cargo clustering in Arabidopsis thaliana
VL - 229
ER -
TY - JOUR
AB - The leaf is a crucial organ evolved with remarkable morphological diversity to maximize plant photosynthesis. The leaf shape is a key trait that affects photosynthesis, flowering rates, disease resistance, and yield. Although many genes regulating leaf development have been identified in the past years, the precise regulatory architecture underlying the generation of diverse leaf shapes remains to be elucidated. We used cotton as a reference model to probe the genetic framework underlying divergent leaf forms. Comparative transcriptome analysis revealed that the GhARF16‐1 and GhKNOX2‐1 genes might be potential regulators of leaf shape. We functionally characterized the auxin‐responsive factor ARF16‐1 acting upstream of GhKNOX2‐1 to determine leaf morphology in cotton. The transcription of GhARF16‐1 was significantly higher in lobed‐leaved cotton than in smooth‐leaved cotton. Furthermore, the overexpression of GhARF16‐1 led to the upregulation of GhKNOX2‐1 and resulted in more and deeper serrations in cotton leaves, similar to the leaf shape of cotton plants overexpressing GhKNOX2‐1. We found that GhARF16‐1 specifically bound to the promoter of GhKNOX2‐1 to induce its expression. The heterologous expression of GhARF16‐1 and GhKNOX2‐1 in Arabidopsis led to lobed and curly leaves, and a genetic analysis revealed that GhKNOX2‐1 is epistatic to GhARF16‐1 in Arabidopsis, suggesting that the GhARF16‐1 and GhKNOX2‐1 interaction paradigm also functions to regulate leaf shape in Arabidopsis. To our knowledge, our results uncover a novel mechanism by which auxin, through the key component ARF16‐1 and its downstream‐activated gene KNOX2‐1, determines leaf morphology in eudicots.
AU - He, P
AU - Zhang, Yuzhou
AU - Li, H
AU - Fu, X
AU - Shang, H
AU - Zou, C
AU - Friml, Jiří
AU - Xiao, G
ID - 8606
IS - 3
JF - Plant Biotechnology Journal
SN - 1467-7644
TI - GhARF16-1 modulates leaf development by transcriptionally regulating the GhKNOX2-1 gene in cotton
VL - 19
ER -
TY - JOUR
AB - The phytohormone auxin plays a central role in shaping plant growth and development. With decades of genetic and biochemical studies, numerous core molecular components and their networks, underlying auxin biosynthesis, transport, and signaling, have been identified. Notably, protein phosphorylation, catalyzed by kinases and oppositely hydrolyzed by phosphatases, has been emerging to be a crucial type of post-translational modification, regulating physiological and developmental auxin output at all levels. In this review, we comprehensively discuss earlier and recent advances in our understanding of genetics, biochemistry, and cell biology of the kinases and phosphatases participating in auxin action. We provide insights into the mechanisms by which reversible protein phosphorylation defines developmental auxin responses, discuss current challenges, and provide our perspectives on future directions involving the integration of the control of protein phosphorylation into the molecular auxin network.
AU - Tan, Shutang
AU - Luschnig, Christian
AU - Friml, Jiří
ID - 8992
IS - 1
JF - Molecular Plant
SN - 16742052
TI - Pho-view of auxin: Reversible protein phosphorylation in auxin biosynthesis, transport and signaling
VL - 14
ER -
TY - JOUR
AB - N-1-naphthylphthalamic acid (NPA) is a key inhibitor of directional (polar) transport of the hormone auxin in plants. For decades, it has been a pivotal tool in elucidating the unique polar auxin transport-based processes underlying plant growth and development. Its exact mode of action has long been sought after and is still being debated, with prevailing mechanistic schemes describing only indirect connections between NPA and the main transporters responsible for directional transport, namely PIN auxin exporters. Here we present data supporting a model in which NPA associates with PINs in a more direct manner than hitherto postulated. We show that NPA inhibits PIN activity in a heterologous oocyte system and that expression of NPA-sensitive PINs in plant, yeast, and oocyte membranes leads to specific saturable NPA binding. We thus propose that PINs are a bona fide NPA target. This offers a straightforward molecular basis for NPA inhibition of PIN-dependent auxin transport and a logical parsimonious explanation for the known physiological effects of NPA on plant growth, as well as an alternative hypothesis to interpret past and future results. We also introduce PIN dimerization and describe an effect of NPA on this, suggesting that NPA binding could be exploited to gain insights into structural aspects of PINs related to their transport mechanism.
AU - Abas, Lindy
AU - Kolb, Martina
AU - Stadlmann, Johannes
AU - Janacek, Dorina P.
AU - Lukic, Kristina
AU - Schwechheimer, Claus
AU - Sazanov, Leonid A
AU - Mach, Lukas
AU - Friml, Jiří
AU - Hammes, Ulrich Z.
ID - 8993
IS - 1
JF - PNAS
SN - 00278424
TI - Naphthylphthalamic acid associates with and inhibits PIN auxin transporters
VL - 118
ER -
TY - JOUR
AB - Auxin is a key regulator of plant growth and development. Local auxin biosynthesis and intercellular transport generates regional gradients in the root that are instructive for processes such as specification of developmental zones that maintain root growth and tropic responses. Here we present a toolbox to study auxin-mediated root development that features: (i) the ability to control auxin synthesis with high spatio-temporal resolution and (ii) single-cell nucleus tracking and morphokinetic analysis infrastructure. Integration of these two features enables cutting-edge analysis of root development at single-cell resolution based on morphokinetic parameters under normal growth conditions and during cell-type-specific induction of auxin biosynthesis. We show directional auxin flow in the root and refine the contributions of key players in this process. In addition, we determine the quantitative kinetics of Arabidopsis root meristem skewing, which depends on local auxin gradients but does not require PIN2 and AUX1 auxin transporter activities. Beyond the mechanistic insights into root development, the tools developed here will enable biologists to study kinetics and morphology of various critical processes at the single cell-level in whole organisms.
AU - Hu, Yangjie
AU - Omary, Moutasem
AU - Hu, Yun
AU - Doron, Ohad
AU - Hörmayer, Lukas
AU - Chen, Qingguo
AU - Megides, Or
AU - Chekli, Ori
AU - Ding, Zhaojun
AU - Friml, Jiří
AU - Zhao, Yunde
AU - Tsarfaty, Ilan
AU - Shani, Eilon
ID - 9254
JF - Nature Communications
TI - Cell kinetics of auxin transport and activity in Arabidopsis root growth and skewing
VL - 12
ER -
TY - JOUR
AB - Endoplasmic reticulum–plasma membrane contact sites (ER–PM CS) play fundamental roles in all eukaryotic cells. Arabidopsis thaliana mutants lacking the ER–PM protein tether synaptotagmin1 (SYT1) exhibit decreased PM integrity under multiple abiotic stresses, such as freezing, high salt, osmotic stress, and mechanical damage. Here, we show that, together with SYT1, the stress-induced SYT3 is an ER–PM tether that also functions in maintaining PM integrity. The ER–PM CS localization of SYT1 and SYT3 is dependent on PM phosphatidylinositol-4-phosphate and is regulated by abiotic stress. Lipidomic analysis revealed that cold stress increased the accumulation of diacylglycerol at the PM in a syt1/3 double mutant relative to wild-type while the levels of most glycerolipid species remain unchanged. In addition, the SYT1-green fluorescent protein fusion preferentially binds diacylglycerol in vivo with little affinity for polar glycerolipids. Our work uncovers a SYT-dependent mechanism of stress adaptation counteracting the detrimental accumulation of diacylglycerol at the PM produced during episodes of abiotic stress.
AU - Ruiz-Lopez, N
AU - Pérez-Sancho, J
AU - Esteban Del Valle, A
AU - Haslam, RP
AU - Vanneste, S
AU - Catalá, R
AU - Perea-Resa, C
AU - Van Damme, D
AU - García-Hernández, S
AU - Albert, A
AU - Vallarino, J
AU - Lin, J
AU - Friml, Jiří
AU - Macho, AP
AU - Salinas, J
AU - Rosado, A
AU - Napier, JA
AU - Amorim-Silva, V
AU - Botella, MA
ID - 9443
IS - 7
JF - Plant Cell
SN - 1040-4651
TI - Synaptotagmins at the endoplasmic reticulum-plasma membrane contact sites maintain diacylglycerol homeostasis during abiotic stress
VL - 33
ER -
TY - JOUR
AB - To overcome nitrogen deficiency, legume roots establish symbiotic interactions with nitrogen-fixing rhizobia that is fostered in specialized organs (nodules). Similar to other organs, nodule formation is determined by a local maximum of the phytohormone auxin at the primordium site. However, how auxin regulates nodule development remains poorly understood. Here, we found that in soybean, (Glycine max), dynamic auxin transport driven by PIN-FORMED (PIN) transporter GmPIN1 is involved in nodule primordium formation. GmPIN1 was specifically expressed in nodule primordium cells and GmPIN1 was polarly localized in these cells. Two nodulation regulators, (iso)flavonoids trigger expanded distribution of GmPIN1b to root cortical cells, and cytokinin rearranges GmPIN1b polarity. Gmpin1abc triple mutants generated with CRISPR-Cas9 showed impaired establishment of auxin maxima in nodule meristems and aberrant divisions in the nodule primordium cells. Moreover, overexpression of GmPIN1 suppressed nodule primordium initiation. GmPIN9d, an ortholog of Arabidopsis thaliana PIN2, acts together with GmPIN1 later in nodule development to acropetally transport auxin in vascular bundles, fine-tuning the auxin supply for nodule enlargement. Our findings reveal how PIN-dependent auxin transport modulates different aspects of soybean nodule development and suggest that establishment of auxin gradient is a prerequisite for the proper interaction between legumes and rhizobia.
AU - Gao, Z
AU - Chen, Z
AU - Cui, Y
AU - Ke, M
AU - Xu, H
AU - Xu, Q
AU - Chen, J
AU - Li, Y
AU - Huang, L
AU - Zhao, H
AU - Huang, D
AU - Mai, S
AU - Xu, T
AU - Liu, X
AU - Li, S
AU - Guan, Y
AU - Yang, W
AU - Friml, Jiří
AU - Petrášek, J
AU - Zhang, J
AU - Chen, X
ID - 9657
IS - 9
JF - Plant Cell
SN - 1040-4651
TI - GmPIN-dependent polar auxin transport is involved in soybean nodule development
VL - 33
ER -
TY - JOUR
AB - Tropisms, growth responses to environmental stimuli such as light or gravity, are spectacular examples of adaptive plant development. The plant hormone auxin serves as a major coordinative signal. The PIN auxin exporters, through their dynamic polar subcellular localizations, redirect auxin fluxes in response to environmental stimuli and the resulting auxin gradients across organs underly differential cell elongation and bending. In this review, we discuss recent advances concerning regulations of PIN polarity during tropisms, focusing on PIN phosphorylation and trafficking. We also cover how environmental cues regulate PIN actions during tropisms, and a crucial role of auxin feedback on PIN polarity during bending termination. Finally, the interactions between different tropisms are reviewed to understand plant adaptive growth in the natural environment.
AU - Han, Huibin
AU - Adamowski, Maciek
AU - Qi, Linlin
AU - Alotaibi, SS
AU - Friml, Jiří
ID - 9656
IS - 2
JF - New Phytologist
SN - 0028-646x
TI - PIN-mediated polar auxin transport regulations in plant tropic responses
VL - 232
ER -
TY - JOUR
AB - Roots are composed of different root types and, in the dicotyledonous Arabidopsis, typically consist of a primary root that branches into lateral roots. Adventitious roots emerge from non-root tissue and are formed upon wounding or other types of abiotic stress. Here, we investigated adventitious root (AR) formation in Arabidopsis hypocotyls under conditions of altered abscisic acid (ABA) signaling. Exogenously applied ABA suppressed AR formation at 0.25 µM or higher doses. AR formation was less sensitive to the synthetic ABA analog pyrabactin (PB). However, PB was a more potent inhibitor at concentrations above 1 µM, suggesting that it was more selective in triggering a root inhibition response. Analysis of a series of phosphonamide and phosphonate pyrabactin analogs suggested that adventitious root formation and lateral root branching are differentially regulated by ABA signaling. ABA biosynthesis and signaling mutants affirmed a general inhibitory role of ABA and point to PYL1 and PYL2 as candidate ABA receptors that regulate AR inhibition.
AU - Zeng, Yinwei
AU - Verstraeten, Inge
AU - Trinh, Hoang Khai
AU - Heugebaert, Thomas
AU - Stevens, Christian V.
AU - Garcia-Maquilon, Irene
AU - Rodriguez, Pedro L.
AU - Vanneste, Steffen
AU - Geelen, Danny
ID - 9909
IS - 8
JF - Genes
TI - Arabidopsis hypocotyl adventitious root formation is suppressed by ABA signaling
VL - 12
ER -
TY - JOUR
AB - Advanced transcriptome sequencing has revealed that the majority of eukaryotic genes undergo alternative splicing (AS). Nonetheless, little effort has been dedicated to investigating the functional relevance of particular splicing events, even those in the key developmental and hormonal regulators. Combining approaches of genetics, biochemistry and advanced confocal microscopy, we describe the impact of alternative splicing on the PIN7 gene in the model plant Arabidopsis thaliana. PIN7 encodes a polarly localized transporter for the phytohormone auxin and produces two evolutionarily conserved transcripts, PIN7a and PIN7b. PIN7a and PIN7b, differing in a four amino acid stretch, exhibit almost identical expression patterns and subcellular localization. We reveal that they are closely associated and mutually influence each other's mobility within the plasma membrane. Phenotypic complementation tests indicate that the functional contribution of PIN7b per se is minor, but it markedly reduces the prominent PIN7a activity, which is required for correct seedling apical hook formation and auxin-mediated tropic responses. Our results establish alternative splicing of the PIN family as a conserved, functionally relevant mechanism, revealing an additional regulatory level of auxin-mediated plant development.
AU - Kashkan, Ivan
AU - Hrtyan, Mónika
AU - Retzer, Katarzyna
AU - Humpolíčková, Jana
AU - Jayasree, Aswathy
AU - Filepová, Roberta
AU - Vondráková, Zuzana
AU - Simon, Sibu
AU - Rombaut, Debbie
AU - Jacobs, Thomas B.
AU - Frilander, Mikko J.
AU - Hejátko, Jan
AU - Friml, Jiří
AU - Petrášek, Jan
AU - Růžička, Kamil
ID - 10282
JF - New Phytologist
SN - 0028-646X
TI - Mutually opposing activity of PIN7 splicing isoforms is required for auxin-mediated tropic responses in Arabidopsis thaliana
VL - 233
ER -
TY - JOUR
AB - Strigolactones (SLs) are carotenoid-derived plant hormones that control shoot branching and communications between host plants and symbiotic fungi or root parasitic plants. Extensive studies have identified the key components participating in SL biosynthesis and signalling, whereas the catabolism or deactivation of endogenous SLs in planta remains largely unknown. Here, we report that the Arabidopsis carboxylesterase 15 (AtCXE15) and its orthologues function as efficient hydrolases of SLs. We show that overexpression of AtCXE15 promotes shoot branching by dampening SL-inhibited axillary bud outgrowth. We further demonstrate that AtCXE15 could bind and efficiently hydrolyse SLs both in vitro and in planta. We also provide evidence that AtCXE15 is capable of catalysing hydrolysis of diverse SL analogues and that such CXE15-dependent catabolism of SLs is evolutionarily conserved in seed plants. These results disclose a catalytic mechanism underlying homoeostatic regulation of SLs in plants, which also provides a rational approach to spatial-temporally manipulate the endogenous SLs and thus architecture of crops and ornamental plants.
AU - Xu, Enjun
AU - Chai, Liang
AU - Zhang, Shiqi
AU - Yu, Ruixue
AU - Zhang, Xixi
AU - Xu, Chongyi
AU - Hu, Yuxin
ID - 10326
JF - Nature Plants
TI - Catabolism of strigolactones by a carboxylesterase
VL - 7
ER -
TY - JOUR
AB - The quality control system for messenger RNA (mRNA) is fundamental for cellular activities in eukaryotes. To elucidate the molecular mechanism of 3'-Phosphoinositide-Dependent Protein Kinase1 (PDK1), a master regulator that is essential throughout eukaryotic growth and development, we employed a forward genetic approach to screen for suppressors of the loss-of-function T-DNA insertion double mutant pdk1.1 pdk1.2 in Arabidopsis thaliana. Notably, the severe growth attenuation of pdk1.1 pdk1.2 was rescued by sop21 (suppressor of pdk1.1 pdk1.2), which harbours a loss-of-function mutation in PELOTA1 (PEL1). PEL1 is a homologue of mammalian PELOTA and yeast (Saccharomyces cerevisiae) DOM34p, which each form a heterodimeric complex with the GTPase HBS1 (HSP70 SUBFAMILY B SUPPRESSOR1, also called SUPERKILLER PROTEIN7, SKI7), a protein that is responsible for ribosomal rescue and thereby assures the quality and fidelity of mRNA molecules during translation. Genetic analysis further revealed that a dysfunctional PEL1-HBS1 complex failed to degrade the T-DNA-disrupted PDK1 transcripts, which were truncated but functional, and thus rescued the growth and developmental defects of pdk1.1 pdk1.2. Our studies demonstrated the functionality of a homologous PELOTA-HBS1 complex and identified its essential regulatory role in plants, providing insights into the mechanism of mRNA quality control.
AU - Kong, W
AU - Tan, Shutang
AU - Zhao, Q
AU - Lin, DL
AU - Xu, ZH
AU - Friml, Jiří
AU - Xue, HW
ID - 9368
IS - 4
JF - Plant Physiology
SN - 0032-0889
TI - mRNA surveillance complex PELOTA-HBS1 eegulates phosphoinositide-sependent protein kinase1 and plant growth
VL - 186
ER -
TY - JOUR
AB - Polar subcellular localization of the PIN exporters of the phytohormone auxin is a key determinant of directional, intercellular auxin transport and thus a central topic of both plant cell and developmental biology. Arabidopsis mutants lacking PID, a kinase that phosphorylates PINs, or the MAB4/MEL proteins of unknown molecular function display PIN polarity defects and phenocopy pin mutants, but mechanistic insights into how these factors convey PIN polarity are missing. Here, by combining protein biochemistry with quantitative live-cell imaging, we demonstrate that PINs, MAB4/MELs, and AGC kinases interact in the same complex at the plasma membrane. MAB4/MELs are recruited to the plasma membrane by the PINs and in concert with the AGC kinases maintain PIN polarity through limiting lateral diffusion-based escape of PINs from the polar domain. The PIN-MAB4/MEL-PID protein complex has self-reinforcing properties thanks to positive feedback between AGC kinase-mediated PIN phosphorylation and MAB4/MEL recruitment. We thus uncover the molecular mechanism by which AGC kinases and MAB4/MEL proteins regulate PIN localization and plant development.
AU - Glanc, Matous
AU - Van Gelderen, K
AU - Hörmayer, Lukas
AU - Tan, Shutang
AU - Naramoto, S
AU - Zhang, Xixi
AU - Domjan, David
AU - Vcelarova, L
AU - Hauschild, Robert
AU - Johnson, Alexander J
AU - de Koning, E
AU - van Dop, M
AU - Rademacher, E
AU - Janson, S
AU - Wei, X
AU - Molnar, Gergely
AU - Fendrych, Matyas
AU - De Rybel, B
AU - Offringa, R
AU - Friml, Jiří
ID - 9290
IS - 9
JF - Current Biology
SN - 0960-9822
TI - AGC kinases and MAB4/MEL proteins maintain PIN polarity by limiting lateral diffusion in plant cells
VL - 31
ER -
TY - JOUR
AB - Plants are able to orient their growth according to gravity, which ultimately controls both shoot and root architecture.1 Gravitropism is a dynamic process whereby gravistimulation induces the asymmetric distribution of the plant hormone auxin, leading to asymmetric growth, organ bending, and subsequent reset of auxin distribution back to the original pre-gravistimulation situation.1, 2, 3 Differential auxin accumulation during the gravitropic response depends on the activity of polarly localized PIN-FORMED (PIN) auxin-efflux carriers.1, 2, 3, 4 In particular, the timing of this dynamic response is regulated by PIN2,5,6 but the underlying molecular mechanisms are poorly understood. Here, we show that MEMBRANE ASSOCIATED KINASE REGULATOR2 (MAKR2) controls the pace of the root gravitropic response. We found that MAKR2 is required for the PIN2 asymmetry during gravitropism by acting as a negative regulator of the cell-surface signaling mediated by the receptor-like kinase TRANSMEMBRANE KINASE1 (TMK1).2,7, 8, 9, 10 Furthermore, we show that the MAKR2 inhibitory effect on TMK1 signaling is antagonized by auxin itself, which triggers rapid MAKR2 membrane dissociation in a TMK1-dependent manner. Our findings suggest that the timing of the root gravitropic response is orchestrated by the reversible inhibition of the TMK1 signaling pathway at the cell surface.
AU - Marquès-Bueno, MM
AU - Armengot, L
AU - Noack, LC
AU - Bareille, J
AU - Rodriguez Solovey, Lesia
AU - Platre, MP
AU - Bayle, V
AU - Liu, M
AU - Opdenacker, D
AU - Vanneste, S
AU - Möller, BK
AU - Nimchuk, ZL
AU - Beeckman, T
AU - Caño-Delgado, AI
AU - Friml, Jiří
AU - Jaillais, Y
ID - 8824
IS - 1
JF - Current Biology
SN - 0960-9822
TI - Auxin-regulated reversible inhibition of TMK1 signaling by MAKR2 modulates the dynamics of root gravitropism
VL - 31
ER -
TY - JOUR
AB - • The phenylpropanoid pathway serves a central role in plant metabolism, providing numerous compounds involved in diverse physiological processes. Most carbon entering the pathway is incorporated into lignin. Although several phenylpropanoid pathway mutants show seedling growth arrest, the role for lignin in seedling growth and development is unexplored.
• We use complementary pharmacological and genetic approaches to block CINNAMATE‐4‐HYDROXYLASE (C4H) functionality in Arabidopsis seedlings and a set of molecular and biochemical techniques to investigate the underlying phenotypes.
• Blocking C4H resulted in reduced lateral rooting and increased adventitious rooting apically in the hypocotyl. These phenotypes coincided with an inhibition in auxin transport. The upstream accumulation in cis‐cinnamic acid was found to likely cause polar auxin transport inhibition. Conversely, a downstream depletion in lignin perturbed phloem‐mediated auxin transport. Restoring lignin deposition effectively reestablished phloem transport and, accordingly, auxin homeostasis.
• Our results show that the accumulation of bioactive intermediates and depletion in lignin jointly cause the aberrant phenotypes upon blocking C4H, and demonstrate that proper deposition of lignin is essential for the establishment of auxin distribution in seedlings. Our data position the phenylpropanoid pathway and lignin in a new physiological framework, consolidating their importance in plant growth and development.
AU - El Houari, I
AU - Van Beirs, C
AU - Arents, HE
AU - Han, Huibin
AU - Chanoca, A
AU - Opdenacker, D
AU - Pollier, J
AU - Storme, V
AU - Steenackers, W
AU - Quareshy, M
AU - Napier, R
AU - Beeckman, T
AU - Friml, Jiří
AU - De Rybel, B
AU - Boerjan, W
AU - Vanholme, B
ID - 9288
IS - 6
JF - New Phytologist
SN - 0028-646x
TI - Seedling developmental defects upon blocking CINNAMATE-4-HYDROXYLASE are caused by perturbations in auxin transport
VL - 230
ER -
TY - JOUR
AB - To adapt to the diverse array of biotic and abiotic cues, plants have evolved sophisticated mechanisms to sense changes in environmental conditions and modulate their growth. Growth-promoting hormones and defence signalling fine tune plant development antagonistically. During host-pathogen interactions, this defence-growth trade-off is mediated by the counteractive effects of the defence hormone salicylic acid (SA) and the growth hormone auxin. Here we revealed an underlying mechanism of SA regulating auxin signalling by constraining the plasma membrane dynamics of PIN2 auxin efflux transporter in Arabidopsis thaliana roots. The lateral diffusion of PIN2 proteins is constrained by SA signalling, during which PIN2 proteins are condensed into hyperclusters depending on REM1.2-mediated nanodomain compartmentalisation. Furthermore, membrane nanodomain compartmentalisation by SA or Remorin (REM) assembly significantly suppressed clathrin-mediated endocytosis. Consequently, SA-induced heterogeneous surface condensation disrupted asymmetric auxin distribution and the resultant gravitropic response. Our results demonstrated a defence-growth trade-off mechanism by which SA signalling crosstalked with auxin transport by concentrating membrane-resident PIN2 into heterogeneous compartments.
AU - Ke, M
AU - Ma, Z
AU - Wang, D
AU - Sun, Y
AU - Wen, C
AU - Huang, D
AU - Chen, Z
AU - Yang, L
AU - Tan, Shutang
AU - Li, R
AU - Friml, Jiří
AU - Miao, Y
AU - Chen, X
ID - 8608
IS - 2
JF - New Phytologist
SN - 0028-646x
TI - Salicylic acid regulates PIN2 auxin transporter hyper-clustering and root gravitropic growth via Remorin-dependent lipid nanodomain organization in Arabidopsis thaliana
VL - 229
ER -
TY - JOUR
AB - In 2008, we published the first set of guidelines for standardizing research in autophagy. Since then, this topic has received increasing attention, and many scientists have entered the field. Our knowledge base and relevant new technologies have also been expanding. Thus, it is important to formulate on a regular basis updated guidelines for monitoring autophagy in different organisms. Despite numerous reviews, there continues to be confusion regarding acceptable methods to evaluate autophagy, especially in multicellular eukaryotes. Here, we present a set of guidelines for investigators to select and interpret methods to examine autophagy and related processes, and for reviewers to provide realistic and reasonable critiques of reports that are focused on these processes. These guidelines are not meant to be a dogmatic set of rules, because the appropriateness of any assay largely depends on the question being asked and the system being used. Moreover, no individual assay is perfect for every situation, calling for the use of multiple techniques to properly monitor autophagy in each experimental setting. Finally, several core components of the autophagy machinery have been implicated in distinct autophagic processes (canonical and noncanonical autophagy), implying that genetic approaches to block autophagy should rely on targeting two or more autophagy-related genes that ideally participate in distinct steps of the pathway. Along similar lines, because multiple proteins involved in autophagy also regulate other cellular pathways including apoptosis, not all of them can be used as a specific marker for bona fide autophagic responses. Here, we critically discuss current methods of assessing autophagy and the information they can, or cannot, provide. Our ultimate goal is to encourage intellectual and technical innovation in the field.
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AU - Fabrias, Gemma
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AU - Facchiano, Francesco
AU - Fadeel, Bengt
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AU - Falcó, Alberto
AU - Falkenburger, Bjorn H.
AU - Fan, Daping
AU - Fan, Jie
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AU - Faure, Mathias
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AU - Fedele, Anthony O.
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AU - Feng, Du
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AU - Feng, Lifeng
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AU - Feng, Yuchen
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AU - Fernández-Veledo, Sonia
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AU - Ferrante, Anthony W.
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AU - Ferreira, Julio C.B.
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AU - Filigheddu, Nicoletta
AU - Filippi-Chiela, Eduardo
AU - Filomeni, Giuseppe
AU - Fimia, Gian Maria
AU - Fineschi, Vittorio
AU - Finetti, Francesca
AU - Finkbeiner, Steven
AU - Fisher, Edward A.
AU - Fisher, Paul B.
AU - Flamigni, Flavio
AU - Fliesler, Steven J.
AU - Flo, Trude H.
AU - Florance, Ida
AU - Florey, Oliver
AU - Florio, Tullio
AU - Fodor, Erika
AU - Follo, Carlo
AU - Fon, Edward A.
AU - Forlino, Antonella
AU - Fornai, Francesco
AU - Fortini, Paola
AU - Fracassi, Anna
AU - Fraldi, Alessandro
AU - Franco, Brunella
AU - Franco, Rodrigo
AU - Franconi, Flavia
AU - Frankel, Lisa B.
AU - Friedman, Scott L.
AU - Fröhlich, Leopold F.
AU - Frühbeck, Gema
AU - Fuentes, Jose M.
AU - Fujiki, Yukio
AU - Fujita, Naonobu
AU - Fujiwara, Yuuki
AU - Fukuda, Mitsunori
AU - Fulda, Simone
AU - Furic, Luc
AU - Furuya, Norihiko
AU - Fusco, Carmela
AU - Gack, Michaela U.
AU - Gaffke, Lidia
AU - Galadari, Sehamuddin
AU - Galasso, Alessia
AU - Galindo, Maria F.
AU - Gallolu Kankanamalage, Sachith
AU - Galluzzi, Lorenzo
AU - Galy, Vincent
AU - Gammoh, Noor
AU - Gan, Boyi
AU - Ganley, Ian G.
AU - Gao, Feng
AU - Gao, Hui
AU - Gao, Minghui
AU - Gao, Ping
AU - Gao, Shou Jiang
AU - Gao, Wentao
AU - Gao, Xiaobo
AU - Garcera, Ana
AU - Garcia, Maria Noé
AU - Garcia, Verónica E.
AU - García-Del Portillo, Francisco
AU - Garcia-Escudero, Vega
AU - Garcia-Garcia, Aracely
AU - Garcia-Macia, Marina
AU - García-Moreno, Diana
AU - Garcia-Ruiz, Carmen
AU - García-Sanz, Patricia
AU - Garg, Abhishek D.
AU - Gargini, Ricardo
AU - Garofalo, Tina
AU - Garry, Robert F.
AU - Gassen, Nils C.
AU - Gatica, Damian
AU - Ge, Liang
AU - Ge, Wanzhong
AU - Geiss-Friedlander, Ruth
AU - Gelfi, Cecilia
AU - Genschik, Pascal
AU - Gentle, Ian E.
AU - Gerbino, Valeria
AU - Gerhardt, Christoph
AU - Germain, Kyla
AU - Germain, Marc
AU - Gewirtz, David A.
AU - Ghasemipour Afshar, Elham
AU - Ghavami, Saeid
AU - Ghigo, Alessandra
AU - Ghosh, Manosij
AU - Giamas, Georgios
AU - Giampietri, Claudia
AU - Giatromanolaki, Alexandra
AU - Gibson, Gary E.
AU - Gibson, Spencer B.
AU - Ginet, Vanessa
AU - Giniger, Edward
AU - Giorgi, Carlotta
AU - Girao, Henrique
AU - Girardin, Stephen E.
AU - Giridharan, Mridhula
AU - Giuliano, Sandy
AU - Giulivi, Cecilia
AU - Giuriato, Sylvie
AU - Giustiniani, Julien
AU - Gluschko, Alexander
AU - Goder, Veit
AU - Goginashvili, Alexander
AU - Golab, Jakub
AU - Goldstone, David C.
AU - Golebiewska, Anna
AU - Gomes, Luciana R.
AU - Gomez, Rodrigo
AU - Gómez-Sánchez, Rubén
AU - Gomez-Puerto, Maria Catalina
AU - Gomez-Sintes, Raquel
AU - Gong, Qingqiu
AU - Goni, Felix M.
AU - González-Gallego, Javier
AU - Gonzalez-Hernandez, Tomas
AU - Gonzalez-Polo, Rosa A.
AU - Gonzalez-Reyes, Jose A.
AU - González-Rodríguez, Patricia
AU - Goping, Ing Swie
AU - Gorbatyuk, Marina S.
AU - Gorbunov, Nikolai V.
AU - Görgülü, Kıvanç
AU - Gorojod, Roxana M.
AU - Gorski, Sharon M.
AU - Goruppi, Sandro
AU - Gotor, Cecilia
AU - Gottlieb, Roberta A.
AU - Gozes, Illana
AU - Gozuacik, Devrim
AU - Graef, Martin
AU - Gräler, Markus H.
AU - Granatiero, Veronica
AU - Grasso, Daniel
AU - Gray, Joshua P.
AU - Green, Douglas R.
AU - Greenhough, Alexander
AU - Gregory, Stephen L.
AU - Griffin, Edward F.
AU - Grinstaff, Mark W.
AU - Gros, Frederic
AU - Grose, Charles
AU - Gross, Angelina S.
AU - Gruber, Florian
AU - Grumati, Paolo
AU - Grune, Tilman
AU - Gu, Xueyan
AU - Guan, Jun Lin
AU - Guardia, Carlos M.
AU - Guda, Kishore
AU - Guerra, Flora
AU - Guerri, Consuelo
AU - Guha, Prasun
AU - Guillén, Carlos
AU - Gujar, Shashi
AU - Gukovskaya, Anna
AU - Gukovsky, Ilya
AU - Gunst, Jan
AU - Günther, Andreas
AU - Guntur, Anyonya R.
AU - Guo, Chuanyong
AU - Guo, Chun
AU - Guo, Hongqing
AU - Guo, Lian Wang
AU - Guo, Ming
AU - Gupta, Pawan
AU - Gupta, Shashi Kumar
AU - Gupta, Swapnil
AU - Gupta, Veer Bala
AU - Gupta, Vivek
AU - Gustafsson, Asa B.
AU - Gutterman, David D.
AU - H.B, Ranjitha
AU - Haapasalo, Annakaisa
AU - Haber, James E.
AU - Hać, Aleksandra
AU - Hadano, Shinji
AU - Hafrén, Anders J.
AU - Haidar, Mansour
AU - Hall, Belinda S.
AU - Halldén, Gunnel
AU - Hamacher-Brady, Anne
AU - Hamann, Andrea
AU - Hamasaki, Maho
AU - Han, Weidong
AU - Hansen, Malene
AU - Hanson, Phyllis I. .
AU - Hao, Zijian
AU - Harada, Masaru
AU - Harhaji-Trajkovic, Ljubica
AU - Hariharan, Nirmala
AU - Haroon, Nigil
AU - Harris, James
AU - Hasegawa, Takafumi
AU - Hasima Nagoor, Noor
AU - Haspel, Jeffrey A.
AU - Haucke, Volker
AU - Hawkins, Wayne D.
AU - Hay, Bruce A.
AU - Haynes, Cole M.
AU - Hayrabedyan, Soren B.
AU - Hays, Thomas S.
AU - He, Congcong
AU - He, Qin
AU - He, Rong Rong
AU - He, You Wen
AU - He, Yu Ying
AU - Heakal, Yasser
AU - Heberle, Alexander M.
AU - Hejtmancik, J. Fielding
AU - Helgason, Gudmundur Vignir
AU - Henkel, Vanessa
AU - Herb, Marc
AU - Hergovich, Alexander
AU - Herman-Antosiewicz, Anna
AU - Hernández, Agustín
AU - Hernandez, Carlos
AU - Hernandez-Diaz, Sergio
AU - Hernandez-Gea, Virginia
AU - Herpin, Amaury
AU - Herreros, Judit
AU - Hervás, Javier H.
AU - Hesselson, Daniel
AU - Hetz, Claudio
AU - Heussler, Volker T.
AU - Higuchi, Yujiro
AU - Hilfiker, Sabine
AU - Hill, Joseph A.
AU - Hlavacek, William S.
AU - Ho, Emmanuel A.
AU - Ho, Idy H.T.
AU - Ho, Philip Wing Lok
AU - Ho, Shu Leong
AU - Ho, Wan Yun
AU - Hobbs, G. Aaron
AU - Hochstrasser, Mark
AU - Hoet, Peter H.M.
AU - Hofius, Daniel
AU - Hofman, Paul
AU - Höhn, Annika
AU - Holmberg, Carina I.
AU - Hombrebueno, Jose R.
AU - Yi-Ren Hong, Chang Won Hong
AU - Hooper, Lora V.
AU - Hoppe, Thorsten
AU - Horos, Rastislav
AU - Hoshida, Yujin
AU - Hsin, I. Lun
AU - Hsu, Hsin Yun
AU - Hu, Bing
AU - Hu, Dong
AU - Hu, Li Fang
AU - Hu, Ming Chang
AU - Hu, Ronggui
AU - Hu, Wei
AU - Hu, Yu Chen
AU - Hu, Zhuo Wei
AU - Hua, Fang
AU - Hua, Jinlian
AU - Hua, Yingqi
AU - Huan, Chongmin
AU - Huang, Canhua
AU - Huang, Chuanshu
AU - Huang, Chuanxin
AU - Huang, Chunling
AU - Huang, Haishan
AU - Huang, Kun
AU - Huang, Michael L.H.
AU - Huang, Rui
AU - Huang, Shan
AU - Huang, Tianzhi
AU - Huang, Xing
AU - Huang, Yuxiang Jack
AU - Huber, Tobias B.
AU - Hubert, Virginie
AU - Hubner, Christian A.
AU - Hughes, Stephanie M.
AU - Hughes, William E.
AU - Humbert, Magali
AU - Hummer, Gerhard
AU - Hurley, James H.
AU - Hussain, Sabah
AU - Hussain, Salik
AU - Hussey, Patrick J.
AU - Hutabarat, Martina
AU - Hwang, Hui Yun
AU - Hwang, Seungmin
AU - Ieni, Antonio
AU - Ikeda, Fumiyo
AU - Imagawa, Yusuke
AU - Imai, Yuzuru
AU - Imbriano, Carol
AU - Imoto, Masaya
AU - Inman, Denise M.
AU - Inoki, Ken
AU - Iovanna, Juan
AU - Iozzo, Renato V.
AU - Ippolito, Giuseppe
AU - Irazoqui, Javier E.
AU - Iribarren, Pablo
AU - Ishaq, Mohd
AU - Ishikawa, Makoto
AU - Ishimwe, Nestor
AU - Isidoro, Ciro
AU - Ismail, Nahed
AU - Issazadeh-Navikas, Shohreh
AU - Itakura, Eisuke
AU - Ito, Daisuke
AU - Ivankovic, Davor
AU - Ivanova, Saška
AU - Iyer, Anand Krishnan V.
AU - Izquierdo, José M.
AU - Izumi, Masanori
AU - Jäättelä, Marja
AU - Jabir, Majid Sakhi
AU - Jackson, William T.
AU - Jacobo-Herrera, Nadia
AU - Jacomin, Anne Claire
AU - Jacquin, Elise
AU - Jadiya, Pooja
AU - Jaeschke, Hartmut
AU - Jagannath, Chinnaswamy
AU - Jakobi, Arjen J.
AU - Jakobsson, Johan
AU - Janji, Bassam
AU - Jansen-Dürr, Pidder
AU - Jansson, Patric J.
AU - Jantsch, Jonathan
AU - Januszewski, Sławomir
AU - Jassey, Alagie
AU - Jean, Steve
AU - Jeltsch-David, Hélène
AU - Jendelova, Pavla
AU - Jenny, Andreas
AU - Jensen, Thomas E.
AU - Jessen, Niels
AU - Jewell, Jenna L.
AU - Ji, Jing
AU - Jia, Lijun
AU - Jia, Rui
AU - Jiang, Liwen
AU - Jiang, Qing
AU - Jiang, Richeng
AU - Jiang, Teng
AU - Jiang, Xuejun
AU - Jiang, Yu
AU - Jimenez-Sanchez, Maria
AU - Jin, Eun Jung
AU - Jin, Fengyan
AU - Jin, Hongchuan
AU - Jin, Li
AU - Jin, Luqi
AU - Jin, Meiyan
AU - Jin, Si
AU - Jo, Eun Kyeong
AU - Joffre, Carine
AU - Johansen, Terje
AU - Johnson, Gail V.W.
AU - Johnston, Simon A.
AU - Jokitalo, Eija
AU - Jolly, Mohit Kumar
AU - Joosten, Leo A.B.
AU - Jordan, Joaquin
AU - Joseph, Bertrand
AU - Ju, Dianwen
AU - Ju, Jeong Sun
AU - Ju, Jingfang
AU - Juárez, Esmeralda
AU - Judith, Delphine
AU - Juhász, Gábor
AU - Jun, Youngsoo
AU - Jung, Chang Hwa
AU - Jung, Sung Chul
AU - Jung, Yong Keun
AU - Jungbluth, Heinz
AU - Jungverdorben, Johannes
AU - Just, Steffen
AU - Kaarniranta, Kai
AU - Kaasik, Allen
AU - Kabuta, Tomohiro
AU - Kaganovich, Daniel
AU - Kahana, Alon
AU - Kain, Renate
AU - Kajimura, Shinjo
AU - Kalamvoki, Maria
AU - Kalia, Manjula
AU - Kalinowski, Danuta S.
AU - Kaludercic, Nina
AU - Kalvari, Ioanna
AU - Kaminska, Joanna
AU - Kaminskyy, Vitaliy O.
AU - Kanamori, Hiromitsu
AU - Kanasaki, Keizo
AU - Kang, Chanhee
AU - Kang, Rui
AU - Kang, Sang Sun
AU - Kaniyappan, Senthilvelrajan
AU - Kanki, Tomotake
AU - Kanneganti, Thirumala Devi
AU - Kanthasamy, Anumantha G.
AU - Kanthasamy, Arthi
AU - Kantorow, Marc
AU - Kapuy, Orsolya
AU - Karamouzis, Michalis V.
AU - Karim, Md Razaul
AU - Karmakar, Parimal
AU - Katare, Rajesh G.
AU - Kato, Masaru
AU - Kaufmann, Stefan H.E.
AU - Kauppinen, Anu
AU - Kaushal, Gur P.
AU - Kaushik, Susmita
AU - Kawasaki, Kiyoshi
AU - Kazan, Kemal
AU - Ke, Po Yuan
AU - Keating, Damien J.
AU - Keber, Ursula
AU - Kehrl, John H.
AU - Keller, Kate E.
AU - Keller, Christian W.
AU - Kemper, Jongsook Kim
AU - Kenific, Candia M.
AU - Kepp, Oliver
AU - Kermorgant, Stephanie
AU - Kern, Andreas
AU - Ketteler, Robin
AU - Keulers, Tom G.
AU - Khalfin, Boris
AU - Khalil, Hany
AU - Khambu, Bilon
AU - Khan, Shahid Y.
AU - Khandelwal, Vinoth Kumar Megraj
AU - Khandia, Rekha
AU - Kho, Widuri
AU - Khobrekar, Noopur V.
AU - Khuansuwan, Sataree
AU - Khundadze, Mukhran
AU - Killackey, Samuel A.
AU - Kim, Dasol
AU - Kim, Deok Ryong
AU - Kim, Do Hyung
AU - Kim, Dong Eun
AU - Kim, Eun Young
AU - Kim, Eun Kyoung
AU - Kim, Hak Rim
AU - Kim, Hee Sik
AU - Hyung-Ryong Kim, Unknown
AU - Kim, Jeong Hun
AU - Kim, Jin Kyung
AU - Kim, Jin Hoi
AU - Kim, Joungmok
AU - Kim, Ju Hwan
AU - Kim, Keun Il
AU - Kim, Peter K.
AU - Kim, Seong Jun
AU - Kimball, Scot R.
AU - Kimchi, Adi
AU - Kimmelman, Alec C.
AU - Kimura, Tomonori
AU - King, Matthew A.
AU - Kinghorn, Kerri J.
AU - Kinsey, Conan G.
AU - Kirkin, Vladimir
AU - Kirshenbaum, Lorrie A.
AU - Kiselev, Sergey L.
AU - Kishi, Shuji
AU - Kitamoto, Katsuhiko
AU - Kitaoka, Yasushi
AU - Kitazato, Kaio
AU - Kitsis, Richard N.
AU - Kittler, Josef T.
AU - Kjaerulff, Ole
AU - Klein, Peter S.
AU - Klopstock, Thomas
AU - Klucken, Jochen
AU - Knævelsrud, Helene
AU - Knorr, Roland L.
AU - Ko, Ben C.B.
AU - Ko, Fred
AU - Ko, Jiunn Liang
AU - Kobayashi, Hotaka
AU - Kobayashi, Satoru
AU - Koch, Ina
AU - Koch, Jan C.
AU - Koenig, Ulrich
AU - Kögel, Donat
AU - Koh, Young Ho
AU - Koike, Masato
AU - Kohlwein, Sepp D.
AU - Kocaturk, Nur M.
AU - Komatsu, Masaaki
AU - König, Jeannette
AU - Kono, Toru
AU - Kopp, Benjamin T.
AU - Korcsmaros, Tamas
AU - Korkmaz, Gözde
AU - Korolchuk, Viktor I.
AU - Korsnes, Mónica Suárez
AU - Koskela, Ali
AU - Kota, Janaiah
AU - Kotake, Yaichiro
AU - Kotler, Monica L.
AU - Kou, Yanjun
AU - Koukourakis, Michael I.
AU - Koustas, Evangelos
AU - Kovacs, Attila L.
AU - Kovács, Tibor
AU - Koya, Daisuke
AU - Kozako, Tomohiro
AU - Kraft, Claudine
AU - Krainc, Dimitri
AU - Krämer, Helmut
AU - Krasnodembskaya, Anna D.
AU - Kretz-Remy, Carole
AU - Kroemer, Guido
AU - Ktistakis, Nicholas T.
AU - Kuchitsu, Kazuyuki
AU - Kuenen, Sabine
AU - Kuerschner, Lars
AU - Kukar, Thomas
AU - Kumar, Ajay
AU - Kumar, Ashok
AU - Kumar, Deepak
AU - Kumar, Dhiraj
AU - Kumar, Sharad
AU - Kume, Shinji
AU - Kumsta, Caroline
AU - Kundu, Chanakya N.
AU - Kundu, Mondira
AU - Kunnumakkara, Ajaikumar B.
AU - Kurgan, Lukasz
AU - Kutateladze, Tatiana G.
AU - Kutlu, Ozlem
AU - Kwak, Seong Ae
AU - Kwon, Ho Jeong
AU - Kwon, Taeg Kyu
AU - Kwon, Yong Tae
AU - Kyrmizi, Irene
AU - La Spada, Albert
AU - Labonté, Patrick
AU - Ladoire, Sylvain
AU - Laface, Ilaria
AU - Lafont, Frank
AU - Lagace, Diane C.
AU - Lahiri, Vikramjit
AU - Lai, Zhibing
AU - Laird, Angela S.
AU - Lakkaraju, Aparna
AU - Lamark, Trond
AU - Lan, Sheng Hui
AU - Landajuela, Ane
AU - Lane, Darius J.R.
AU - Lane, Jon D.
AU - Lang, Charles H.
AU - Lange, Carsten
AU - Langel, Ülo
AU - Langer, Rupert
AU - Lapaquette, Pierre
AU - Laporte, Jocelyn
AU - Larusso, Nicholas F.
AU - Lastres-Becker, Isabel
AU - Lau, Wilson Chun Yu
AU - Laurie, Gordon W.
AU - Lavandero, Sergio
AU - Law, Betty Yuen Kwan
AU - Law, Helen Ka Wai
AU - Layfield, Rob
AU - Le, Weidong
AU - Le Stunff, Herve
AU - Leary, Alexandre Y.
AU - Lebrun, Jean Jacques
AU - Leck, Lionel Y.W.
AU - Leduc-Gaudet, Jean Philippe
AU - Lee, Changwook
AU - Lee, Chung Pei
AU - Lee, Da Hye
AU - Lee, Edward B.
AU - Lee, Erinna F.
AU - Lee, Gyun Min
AU - Lee, He Jin
AU - Lee, Heung Kyu
AU - Lee, Jae Man
AU - Lee, Jason S.
AU - Lee, Jin A.
AU - Lee, Joo Yong
AU - Lee, Jun Hee
AU - Lee, Michael
AU - Lee, Min Goo
AU - Lee, Min Jae
AU - Lee, Myung Shik
AU - Lee, Sang Yoon
AU - Lee, Seung Jae
AU - Lee, Stella Y.
AU - Lee, Sung Bae
AU - Lee, Won Hee
AU - Lee, Ying Ray
AU - Lee, Yong Ho
AU - Lee, Youngil
AU - Lefebvre, Christophe
AU - Legouis, Renaud
AU - Lei, Yu L.
AU - Lei, Yuchen
AU - Leikin, Sergey
AU - Leitinger, Gerd
AU - Lemus, Leticia
AU - Leng, Shuilong
AU - Lenoir, Olivia
AU - Lenz, Guido
AU - Lenz, Heinz Josef
AU - Lenzi, Paola
AU - León, Yolanda
AU - Leopoldino, Andréia M.
AU - Leschczyk, Christoph
AU - Leskelä, Stina
AU - Letellier, Elisabeth
AU - Leung, Chi Ting
AU - Leung, Po Sing
AU - Leventhal, Jeremy S.
AU - Levine, Beth
AU - Lewis, Patrick A.
AU - Ley, Klaus
AU - Li, Bin
AU - Li, Da Qiang
AU - Li, Jianming
AU - Li, Jing
AU - Li, Jiong
AU - Li, Ke
AU - Li, Liwu
AU - Li, Mei
AU - Li, Min
AU - Li, Min
AU - Li, Ming
AU - Li, Mingchuan
AU - Li, Pin Lan
AU - Li, Ming Qing
AU - Li, Qing
AU - Li, Sheng
AU - Li, Tiangang
AU - Li, Wei
AU - Li, Wenming
AU - Li, Xue
AU - Li, Yi Ping
AU - Li, Yuan
AU - Li, Zhiqiang
AU - Li, Zhiyong
AU - Li, Zhiyuan
AU - Lian, Jiqin
AU - Liang, Chengyu
AU - Liang, Qiangrong
AU - Liang, Weicheng
AU - Liang, Yongheng
AU - Liang, Yong Tian
AU - Liao, Guanghong
AU - Liao, Lujian
AU - Liao, Mingzhi
AU - Liao, Yung Feng
AU - Librizzi, Mariangela
AU - Lie, Pearl P.Y.
AU - Lilly, Mary A.
AU - Lim, Hyunjung J.
AU - Lima, Thania R.R.
AU - Limana, Federica
AU - Lin, Chao
AU - Lin, Chih Wen
AU - Lin, Dar Shong
AU - Lin, Fu Cheng
AU - Lin, Jiandie D.
AU - Lin, Kurt M.
AU - Lin, Kwang Huei
AU - Lin, Liang Tzung
AU - Lin, Pei Hui
AU - Lin, Qiong
AU - Lin, Shaofeng
AU - Lin, Su Ju
AU - Lin, Wenyu
AU - Lin, Xueying
AU - Lin, Yao Xin
AU - Lin, Yee Shin
AU - Linden, Rafael
AU - Lindner, Paula
AU - Ling, Shuo Chien
AU - Lingor, Paul
AU - Linnemann, Amelia K.
AU - Liou, Yih Cherng
AU - Lipinski, Marta M.
AU - Lipovšek, Saška
AU - Lira, Vitor A.
AU - Lisiak, Natalia
AU - Liton, Paloma B.
AU - Liu, Chao
AU - Liu, Ching Hsuan
AU - Liu, Chun Feng
AU - Liu, Cui Hua
AU - Liu, Fang
AU - Liu, Hao
AU - Liu, Hsiao Sheng
AU - Liu, Hua Feng
AU - Liu, Huifang
AU - Liu, Jia
AU - Liu, Jing
AU - Liu, Julia
AU - Liu, Leyuan
AU - Liu, Longhua
AU - Liu, Meilian
AU - Liu, Qin
AU - Liu, Wei
AU - Liu, Wende
AU - Liu, Xiao Hong
AU - Liu, Xiaodong
AU - Liu, Xingguo
AU - Liu, Xu
AU - Liu, Xuedong
AU - Liu, Yanfen
AU - Liu, Yang
AU - Liu, Yang
AU - Liu, Yueyang
AU - Liu, Yule
AU - Livingston, J. Andrew
AU - Lizard, Gerard
AU - Lizcano, Jose M.
AU - Ljubojevic-Holzer, Senka
AU - Lleonart, Matilde E.
AU - Llobet-Navàs, David
AU - Llorente, Alicia
AU - Lo, Chih Hung
AU - Lobato-Márquez, Damián
AU - Long, Qi
AU - Long, Yun Chau
AU - Loos, Ben
AU - Loos, Julia A.
AU - López, Manuela G.
AU - López-Doménech, Guillermo
AU - López-Guerrero, José Antonio
AU - López-Jiménez, Ana T.
AU - López-Pérez, Óscar
AU - López-Valero, Israel
AU - Lorenowicz, Magdalena J.
AU - Lorente, Mar
AU - Lorincz, Peter
AU - Lossi, Laura
AU - Lotersztajn, Sophie
AU - Lovat, Penny E.
AU - Lovell, Jonathan F.
AU - Lovy, Alenka
AU - Lőw, Péter
AU - Lu, Guang
AU - Lu, Haocheng
AU - Lu, Jia Hong
AU - Lu, Jin Jian
AU - Lu, Mengji
AU - Lu, Shuyan
AU - Luciani, Alessandro
AU - Lucocq, John M.
AU - Ludovico, Paula
AU - Luftig, Micah A.
AU - Luhr, Morten
AU - Luis-Ravelo, Diego
AU - Lum, Julian J.
AU - Luna-Dulcey, Liany
AU - Lund, Anders H.
AU - Lund, Viktor K.
AU - Lünemann, Jan D.
AU - Lüningschrör, Patrick
AU - Luo, Honglin
AU - Luo, Rongcan
AU - Luo, Shouqing
AU - Luo, Zhi
AU - Luparello, Claudio
AU - Lüscher, Bernhard
AU - Luu, Luan
AU - Lyakhovich, Alex
AU - Lyamzaev, Konstantin G.
AU - Lystad, Alf Håkon
AU - Lytvynchuk, Lyubomyr
AU - Ma, Alvin C.
AU - Ma, Changle
AU - Ma, Mengxiao
AU - Ma, Ning Fang
AU - Ma, Quan Hong
AU - Ma, Xinliang
AU - Ma, Yueyun
AU - Ma, Zhenyi
AU - Macdougald, Ormond A.
AU - Macian, Fernando
AU - Macintosh, Gustavo C.
AU - Mackeigan, Jeffrey P.
AU - Macleod, Kay F.
AU - Maday, Sandra
AU - Madeo, Frank
AU - Madesh, Muniswamy
AU - Madl, Tobias
AU - Madrigal-Matute, Julio
AU - Maeda, Akiko
AU - Maejima, Yasuhiro
AU - Magarinos, Marta
AU - Mahavadi, Poornima
AU - Maiani, Emiliano
AU - Maiese, Kenneth
AU - Maiti, Panchanan
AU - Maiuri, Maria Chiara
AU - Majello, Barbara
AU - Major, Michael B.
AU - Makareeva, Elena
AU - Malik, Fayaz
AU - Mallilankaraman, Karthik
AU - Malorni, Walter
AU - Maloyan, Alina
AU - Mammadova, Najiba
AU - Man, Gene Chi Wai
AU - Manai, Federico
AU - Mancias, Joseph D.
AU - Mandelkow, Eva Maria
AU - Mandell, Michael A.
AU - Manfredi, Angelo A.
AU - Manjili, Masoud H.
AU - Manjithaya, Ravi
AU - Manque, Patricio
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AU - Manzoni, Claudia
AU - Mao, Kai
AU - Marchese, Cinzia
AU - Marchetti, Sandrine
AU - Marconi, Anna Maria
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AU - Mari, Muriel
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AU - Marinelli, Oliviero
AU - Mariño, Guillermo
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AU - Martin, Sara
AU - Martin, Shaun
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AU - Martinez, Jennifer
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AU - Massieu, Lourdes
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AU - Moley, Kelle H.
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AU - Moreno, Sandra
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AU - Morgan, Alwena H.
AU - Morin, Fabrice
AU - Morishita, Hideaki
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AU - Moriyama, Mariko
AU - Moriyasu, Yuji
AU - Morleo, Manuela
AU - Morselli, Eugenia
AU - Moruno-Manchon, Jose F.
AU - Moscat, Jorge
AU - Mostowy, Serge
AU - Motori, Elisa
AU - Moura, Andrea Felinto
AU - Moustaid-Moussa, Naima
AU - Mrakovcic, Maria
AU - Muciño-Hernández, Gabriel
AU - Mukherjee, Anupam
AU - Mukhopadhyay, Subhadip
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AU - Mulero, Victoriano
AU - Muller, Sylviane
AU - Münch, Christian
AU - Munjal, Ashok
AU - Munoz-Canoves, Pura
AU - Muñoz-Galdeano, Teresa
AU - Münz, Christian
AU - Murakawa, Tomokazu
AU - Muratori, Claudia
AU - Murphy, Brona M.
AU - Murphy, J. Patrick
AU - Murthy, Aditya
AU - Myöhänen, Timo T.
AU - Mysorekar, Indira U.
AU - Mytych, Jennifer
AU - Nabavi, Seyed Mohammad
AU - Nabissi, Massimo
AU - Nagy, Péter
AU - Nah, Jihoon
AU - Nahimana, Aimable
AU - Nakagawa, Ichiro
AU - Nakamura, Ken
AU - Nakatogawa, Hitoshi
AU - Nandi, Shyam S.
AU - Nanjundan, Meera
AU - Nanni, Monica
AU - Napolitano, Gennaro
AU - Nardacci, Roberta
AU - Narita, Masashi
AU - Nassif, Melissa
AU - Nathan, Ilana
AU - Natsumeda, Manabu
AU - Naude, Ryno J.
AU - Naumann, Christin
AU - Naveiras, Olaia
AU - Navid, Fatemeh
AU - Nawrocki, Steffan T.
AU - Nazarko, Taras Y.
AU - Nazio, Francesca
AU - Negoita, Florentina
AU - Neill, Thomas
AU - Neisch, Amanda L.
AU - Neri, Luca M.
AU - Netea, Mihai G.
AU - Neubert, Patrick
AU - Neufeld, Thomas P.
AU - Neumann, Dietbert
AU - Neutzner, Albert
AU - Newton, Phillip T.
AU - Ney, Paul A.
AU - Nezis, Ioannis P.
AU - Ng, Charlene C.W.
AU - Ng, Tzi Bun
AU - Nguyen, Hang T.T.
AU - Nguyen, Long T.
AU - Ni, Hong Min
AU - Ní Cheallaigh, Clíona
AU - Ni, Zhenhong
AU - Nicolao, M. Celeste
AU - Nicoli, Francesco
AU - Nieto-Diaz, Manuel
AU - Nilsson, Per
AU - Ning, Shunbin
AU - Niranjan, Rituraj
AU - Nishimune, Hiroshi
AU - Niso-Santano, Mireia
AU - Nixon, Ralph A.
AU - Nobili, Annalisa
AU - Nobrega, Clevio
AU - Noda, Takeshi
AU - Nogueira-Recalde, Uxía
AU - Nolan, Trevor M.
AU - Nombela, Ivan
AU - Novak, Ivana
AU - Novoa, Beatriz
AU - Nozawa, Takashi
AU - Nukina, Nobuyuki
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AU - Ogmundsdottir, Margret H.
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AU - Oh, Goo Taeg
AU - Oh, Seon Hee
AU - Oh, Young J.
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AU - Ohashi, Yohei
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AU - Okazawa, Hitoshi
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AU - Ott, Christiane
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AU - Pallet, Nicolas
AU - Palmieri, Michela
AU - Palmisano, Giuseppe
AU - Palumbo, Camilla
AU - Pampaloni, Francesco
AU - Pan, Lifeng
AU - Pan, Qingjun
AU - Pan, Wenliang
AU - Pan, Xin
AU - Panasyuk, Ganna
AU - Pandey, Rahul
AU - Pandey, Udai B.
AU - Pandya, Vrajesh
AU - Paneni, Francesco
AU - Pang, Shirley Y.
AU - Panzarini, Elisa
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AU - Papinski, Daniel
AU - Papp, Diana
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AU - Park, Hwan Tae
AU - Park, Ji Man
AU - Park, Jong In
AU - Park, Joon Tae
AU - Park, Junsoo
AU - Park, Sang Chul
AU - Park, Sang Youel
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AU - Pasquier, Adrien
AU - Pasquier, Benoit
AU - Passos, João F.
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AU - Patel, Hemal H.
AU - Patschan, Daniel
AU - Pattingre, Sophie
AU - Pedraza-Alva, Gustavo
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AU - Pedrozo, Zully
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AU - Pei, Jianming
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AU - Peng, Ying
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AU - Pennuto, Maria
AU - Pentimalli, Francesca
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AU - Pereira, Gustavo J.S.
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AU - Perrotta, Cristiana
AU - Perrotta, Ida
AU - Pestell, Richard G.
AU - Petersen, Morten
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AU - Petrovski, Goran
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AU - Pfister, Astrid S.
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AU - Pickrell, Alicia M.
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AU - Pierre, Philippe
AU - Pierrefite-Carle, Valérie
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AU - Pimentel-Muiños, Felipe X.
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AU - Pinheiro, Roberta O.
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AU - Pircs, Karolina
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AU - Pizzo, Paola
AU - Plantinga, Theo S.
AU - Platta, Harald W.
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AU - Plotnikov, Egor Y.
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AU - Pluta, Ryszard
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AU - Pöggeler, Stefanie
AU - Pohl, Christian
AU - Poirot, Marc
AU - Poletti, Angelo
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AU - Popova, Blagovesta
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AU - Potts, Malia B.
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AU - Quarleri, Jorge
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AU - Rabinowich, Hannah
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AU - Rao, Lang
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AU - Ratovitski, Edward A.
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AU - Reiling, Jan H.
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AU - Reipert, Siegfried
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AU - Ren, Jun
AU - Ren, Weichao
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AU - Reue, Karen
AU - Rewitz, Kim
AU - Ribeiro De Andrade Ramos, Bruna
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AU - Riccio, Victoria
AU - Richardson, Des R.
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AU - Rizzuto, Rosario
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AU - Roberts, Luke D.
AU - Robinson, Katherine J.
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AU - Rocchi, Stephane
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AU - Rodrigues, Tiago
AU - Rodrigues Silva, Vagner Ramon
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AU - Rogov, Vladimir V.
AU - Rojo, Ana I.
AU - Rolka, Krzysztof
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AU - Romano, Patricia S.
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AU - Romero, Luis C.
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AU - Rongo, Christopher
AU - Roperto, Sante
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AU - Rosenstiel, Philip
AU - Rosenwald, Anne G.
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AU - Roth, Lynn
AU - Roth, Steven
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AU - Rovere-Querini, Patrizia
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AU - Rubtsova, Maria P.
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AU - Ruckenstuhl, Christoph
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AU - Rudolf, Rüdiger
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AU - Rusmini, Paola
AU - Russell, Ryan R.
AU - Russo, Gian Luigi
AU - Russo, Maria
AU - Russo, Rossella
AU - Ryabaya, Oxana O.
AU - Ryan, Kevin M.
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AU - Sabater-Arcis, Maria
AU - Sachdev, Ulka
AU - Sacher, Michael
AU - Sachse, Carsten
AU - Sadhu, Abhishek
AU - Sadoshima, Junichi
AU - Safren, Nathaniel
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AU - Sagona, Antonia P.
AU - Sahay, Gaurav
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AU - Sahin, Ozgur
AU - Sahni, Sumit
AU - Saito, Nayuta
AU - Saito, Shigeru
AU - Saito, Tsunenori
AU - Sakai, Ryohei
AU - Sakai, Yasuyoshi
AU - Sakamaki, Jun Ichi
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AU - Salazar, Gloria
AU - Salazar-Degracia, Anna
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AU - Sancho-Shimizu, Vanessa
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AU - Santaguida, Stefano
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AU - Sanz, Pascual
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AU - Sardiello, Marco
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AU - Sarrias, Maria Rosa
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AU - Schlattner, Uwe
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AU - Schmitt, Roland
AU - Schmidt, Stephen D.
AU - Schmitz, Ingo
AU - Schmukler, Eran
AU - Schneider, Anja
AU - Schneider, Bianca E.
AU - Schober, Romana
AU - Schoijet, Alejandra C.
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AU - Schramm, Michael
AU - Schröder, Bernd
AU - Schuh, Kai
AU - Schüller, Christoph
AU - Schulze, Ryan J.
AU - Schürmanns, Lea
AU - Schwamborn, Jens C.
AU - Schwarten, Melanie
AU - Scialo, Filippo
AU - Sciarretta, Sebastiano
AU - Scott, Melanie J.
AU - Scotto, Kathleen W.
AU - Scovassi, A. Ivana
AU - Scrima, Andrea
AU - Scrivo, Aurora
AU - Sebastian, David
AU - Sebti, Salwa
AU - Sedej, Simon
AU - Segatori, Laura
AU - Segev, Nava
AU - Seglen, Per O.
AU - Seiliez, Iban
AU - Seki, Ekihiro
AU - Selleck, Scott B.
AU - Sellke, Frank W.
AU - Selsby, Joshua T.
AU - Sendtner, Michael
AU - Senturk, Serif
AU - Seranova, Elena
AU - Sergi, Consolato
AU - Serra-Moreno, Ruth
AU - Sesaki, Hiromi
AU - Settembre, Carmine
AU - Setty, Subba Rao Gangi
AU - Sgarbi, Gianluca
AU - Sha, Ou
AU - Shacka, John J.
AU - Shah, Javeed A.
AU - Shang, Dantong
AU - Shao, Changshun
AU - Shao, Feng
AU - Sharbati, Soroush
AU - Sharkey, Lisa M.
AU - Sharma, Dipali
AU - Sharma, Gaurav
AU - Sharma, Kulbhushan
AU - Sharma, Pawan
AU - Sharma, Surendra
AU - Shen, Han Ming
AU - Shen, Hongtao
AU - Shen, Jiangang
AU - Shen, Ming
AU - Shen, Weili
AU - Shen, Zheni
AU - Sheng, Rui
AU - Sheng, Zhi
AU - Sheng, Zu Hang
AU - Shi, Jianjian
AU - Shi, Xiaobing
AU - Shi, Ying Hong
AU - Shiba-Fukushima, Kahori
AU - Shieh, Jeng Jer
AU - Shimada, Yohta
AU - Shimizu, Shigeomi
AU - Shimozawa, Makoto
AU - Shintani, Takahiro
AU - Shoemaker, Christopher J.
AU - Shojaei, Shahla
AU - Shoji, Ikuo
AU - Shravage, Bhupendra V.
AU - Shridhar, Viji
AU - Shu, Chih Wen
AU - Shu, Hong Bing
AU - Shui, Ke
AU - Shukla, Arvind K.
AU - Shutt, Timothy E.
AU - Sica, Valentina
AU - Siddiqui, Aleem
AU - Sierra, Amanda
AU - Sierra-Torre, Virginia
AU - Signorelli, Santiago
AU - Sil, Payel
AU - Silva, Bruno J.De Andrade
AU - Silva, Johnatas D.
AU - Silva-Pavez, Eduardo
AU - Silvente-Poirot, Sandrine
AU - Simmonds, Rachel E.
AU - Simon, Anna Katharina
AU - Simon, Hans Uwe
AU - Simons, Matias
AU - Singh, Anurag
AU - Singh, Lalit P.
AU - Singh, Rajat
AU - Singh, Shivendra V.
AU - Singh, Shrawan K.
AU - Singh, Sudha B.
AU - Singh, Sunaina
AU - Singh, Surinder Pal
AU - Sinha, Debasish
AU - Sinha, Rohit Anthony
AU - Sinha, Sangita
AU - Sirko, Agnieszka
AU - Sirohi, Kapil
AU - Sivridis, Efthimios L.
AU - Skendros, Panagiotis
AU - Skirycz, Aleksandra
AU - Slaninová, Iva
AU - Smaili, Soraya S.
AU - Smertenko, Andrei
AU - Smith, Matthew D.
AU - Soenen, Stefaan J.
AU - Sohn, Eun Jung
AU - Sok, Sophia P.M.
AU - Solaini, Giancarlo
AU - Soldati, Thierry
AU - Soleimanpour, Scott A.
AU - Soler, Rosa M.
AU - Solovchenko, Alexei
AU - Somarelli, Jason A.
AU - Sonawane, Avinash
AU - Song, Fuyong
AU - Song, Hyun Kyu
AU - Song, Ju Xian
AU - Song, Kunhua
AU - Song, Zhiyin
AU - Soria, Leandro R.
AU - Sorice, Maurizio
AU - Soukas, Alexander A.
AU - Soukup, Sandra Fausia
AU - Sousa, Diana
AU - Sousa, Nadia
AU - Spagnuolo, Paul A.
AU - Spector, Stephen A.
AU - Srinivas Bharath, M. M.
AU - St. Clair, Daret
AU - Stagni, Venturina
AU - Staiano, Leopoldo
AU - Stalnecker, Clint A.
AU - Stankov, Metodi V.
AU - Stathopulos, Peter B.
AU - Stefan, Katja
AU - Stefan, Sven Marcel
AU - Stefanis, Leonidas
AU - Steffan, Joan S.
AU - Steinkasserer, Alexander
AU - Stenmark, Harald
AU - Sterneckert, Jared
AU - Stevens, Craig
AU - Stoka, Veronika
AU - Storch, Stephan
AU - Stork, Björn
AU - Strappazzon, Flavie
AU - Strohecker, Anne Marie
AU - Stupack, Dwayne G.
AU - Su, Huanxing
AU - Su, Ling Yan
AU - Su, Longxiang
AU - Suarez-Fontes, Ana M.
AU - Subauste, Carlos S.
AU - Subbian, Selvakumar
AU - Subirada, Paula V.
AU - Sudhandiran, Ganapasam
AU - Sue, Carolyn M.
AU - Sui, Xinbing
AU - Summers, Corey
AU - Sun, Guangchao
AU - Sun, Jun
AU - Sun, Kang
AU - Sun, Meng Xiang
AU - Sun, Qiming
AU - Sun, Yi
AU - Sun, Zhongjie
AU - Sunahara, Karen K.S.
AU - Sundberg, Eva
AU - Susztak, Katalin
AU - Sutovsky, Peter
AU - Suzuki, Hidekazu
AU - Sweeney, Gary
AU - Symons, J. David
AU - Sze, Stephen Cho Wing
AU - Szewczyk, Nathaniel J.
AU - Tabęcka-Łonczynska, Anna
AU - Tabolacci, Claudio
AU - Tacke, Frank
AU - Taegtmeyer, Heinrich
AU - Tafani, Marco
AU - Tagaya, Mitsuo
AU - Tai, Haoran
AU - Tait, Stephen W.G.
AU - Takahashi, Yoshinori
AU - Takats, Szabolcs
AU - Talwar, Priti
AU - Tam, Chit
AU - Tam, Shing Yau
AU - Tampellini, Davide
AU - Tamura, Atsushi
AU - Tan, Chong Teik
AU - Tan, Eng King
AU - Tan, Ya Qin
AU - Tanaka, Masaki
AU - Tanaka, Motomasa
AU - Tang, Daolin
AU - Tang, Jingfeng
AU - Tang, Tie Shan
AU - Tanida, Isei
AU - Tao, Zhipeng
AU - Taouis, Mohammed
AU - Tatenhorst, Lars
AU - Tavernarakis, Nektarios
AU - Taylor, Allen
AU - Taylor, Gregory A.
AU - Taylor, Joan M.
AU - Tchetina, Elena
AU - Tee, Andrew R.
AU - Tegeder, Irmgard
AU - Teis, David
AU - Teixeira, Natercia
AU - Teixeira-Clerc, Fatima
AU - Tekirdag, Kumsal A.
AU - Tencomnao, Tewin
AU - Tenreiro, Sandra
AU - Tepikin, Alexei V.
AU - Testillano, Pilar S.
AU - Tettamanti, Gianluca
AU - Tharaux, Pierre Louis
AU - Thedieck, Kathrin
AU - Thekkinghat, Arvind A.
AU - Thellung, Stefano
AU - Thinwa, Josephine W.
AU - Thirumalaikumar, V. P.
AU - Thomas, Sufi Mary
AU - Thomes, Paul G.
AU - Thorburn, Andrew
AU - Thukral, Lipi
AU - Thum, Thomas
AU - Thumm, Michael
AU - Tian, Ling
AU - Tichy, Ales
AU - Till, Andreas
AU - Timmerman, Vincent
AU - Titorenko, Vladimir I.
AU - Todi, Sokol V.
AU - Todorova, Krassimira
AU - Toivonen, Janne M.
AU - Tomaipitinca, Luana
AU - Tomar, Dhanendra
AU - Tomas-Zapico, Cristina
AU - Tomić, Sergej
AU - Tong, Benjamin Chun Kit
AU - Tong, Chao
AU - Tong, Xin
AU - Tooze, Sharon A.
AU - Torgersen, Maria L.
AU - Torii, Satoru
AU - Torres-López, Liliana
AU - Torriglia, Alicia
AU - Towers, Christina G.
AU - Towns, Roberto
AU - Toyokuni, Shinya
AU - Trajkovic, Vladimir
AU - Tramontano, Donatella
AU - Tran, Quynh Giao
AU - Travassos, Leonardo H.
AU - Trelford, Charles B.
AU - Tremel, Shirley
AU - Trougakos, Ioannis P.
AU - Tsao, Betty P.
AU - Tschan, Mario P.
AU - Tse, Hung Fat
AU - Tse, Tak Fu
AU - Tsugawa, Hitoshi
AU - Tsvetkov, Andrey S.
AU - Tumbarello, David A.
AU - Tumtas, Yasin
AU - Tuñón, María J.
AU - Turcotte, Sandra
AU - Turk, Boris
AU - Turk, Vito
AU - Turner, Bradley J.
AU - Tuxworth, Richard I.
AU - Tyler, Jessica K.
AU - Tyutereva, Elena V.
AU - Uchiyama, Yasuo
AU - Ugun-Klusek, Aslihan
AU - Uhlig, Holm H.
AU - Ułamek-Kozioł, Marzena
AU - Ulasov, Ilya V.
AU - Umekawa, Midori
AU - Ungermann, Christian
AU - Unno, Rei
AU - Urbe, Sylvie
AU - Uribe-Carretero, Elisabet
AU - Üstün, Suayib
AU - Uversky, Vladimir N.
AU - Vaccari, Thomas
AU - Vaccaro, Maria I.
AU - Vahsen, Björn F.
AU - Vakifahmetoglu-Norberg, Helin
AU - Valdor, Rut
AU - Valente, Maria J.
AU - Valko, Ayelén
AU - Vallee, Richard B.
AU - Valverde, Angela M.
AU - Van Den Berghe, Greet
AU - Van Der Veen, Stijn
AU - Van Kaer, Luc
AU - Van Loosdregt, Jorg
AU - Van Wijk, Sjoerd J.L.
AU - Vandenberghe, Wim
AU - Vanhorebeek, Ilse
AU - Vannier-Santos, Marcos A.
AU - Vannini, Nicola
AU - Vanrell, M. Cristina
AU - Vantaggiato, Chiara
AU - Varano, Gabriele
AU - Varela-Nieto, Isabel
AU - Varga, Máté
AU - Vasconcelos, M. Helena
AU - Vats, Somya
AU - Vavvas, Demetrios G.
AU - Vega-Naredo, Ignacio
AU - Vega-Rubin-De-Celis, Silvia
AU - Velasco, Guillermo
AU - Velázquez, Ariadna P.
AU - Vellai, Tibor
AU - Vellenga, Edo
AU - Velotti, Francesca
AU - Verdier, Mireille
AU - Verginis, Panayotis
AU - Vergne, Isabelle
AU - Verkade, Paul
AU - Verma, Manish
AU - Verstreken, Patrik
AU - Vervliet, Tim
AU - Vervoorts, Jörg
AU - Vessoni, Alexandre T.
AU - Victor, Victor M.
AU - Vidal, Michel
AU - Vidoni, Chiara
AU - Vieira, Otilia V.
AU - Vierstra, Richard D.
AU - Viganó, Sonia
AU - Vihinen, Helena
AU - Vijayan, Vinoy
AU - Vila, Miquel
AU - Vilar, Marçal
AU - Villalba, José M.
AU - Villalobo, Antonio
AU - Villarejo-Zori, Beatriz
AU - Villarroya, Francesc
AU - Villarroya, Joan
AU - Vincent, Olivier
AU - Vindis, Cecile
AU - Viret, Christophe
AU - Viscomi, Maria Teresa
AU - Visnjic, Dora
AU - Vitale, Ilio
AU - Vocadlo, David J.
AU - Voitsekhovskaja, Olga V.
AU - Volonté, Cinzia
AU - Volta, Mattia
AU - Vomero, Marta
AU - Von Haefen, Clarissa
AU - Vooijs, Marc A.
AU - Voos, Wolfgang
AU - Vucicevic, Ljubica
AU - Wade-Martins, Richard
AU - Waguri, Satoshi
AU - Waite, Kenrick A.
AU - Wakatsuki, Shuji
AU - Walker, David W.
AU - Walker, Mark J.
AU - Walker, Simon A.
AU - Walter, Jochen
AU - Wandosell, Francisco G.
AU - Wang, Bo
AU - Wang, Chao Yung
AU - Wang, Chen
AU - Wang, Chenran
AU - Wang, Chenwei
AU - Wang, Cun Yu
AU - Wang, Dong
AU - Wang, Fangyang
AU - Wang, Feng
AU - Wang, Fengming
AU - Wang, Guansong
AU - Wang, Han
AU - Wang, Hao
AU - Wang, Hexiang
AU - Wang, Hong Gang
AU - Wang, Jianrong
AU - Wang, Jigang
AU - Wang, Jiou
AU - Wang, Jundong
AU - Wang, Kui
AU - Wang, Lianrong
AU - Wang, Liming
AU - Wang, Maggie Haitian
AU - Wang, Meiqing
AU - Wang, Nanbu
AU - Wang, Pengwei
AU - Wang, Peipei
AU - Wang, Ping
AU - Wang, Ping
AU - Wang, Qing Jun
AU - Wang, Qing
AU - Wang, Qing Kenneth
AU - Wang, Qiong A.
AU - Wang, Wen Tao
AU - Wang, Wuyang
AU - Wang, Xinnan
AU - Wang, Xuejun
AU - Wang, Yan
AU - Wang, Yanchang
AU - Wang, Yanzhuang
AU - Wang, Yen Yun
AU - Wang, Yihua
AU - Wang, Yipeng
AU - Wang, Yu
AU - Wang, Yuqi
AU - Wang, Zhe
AU - Wang, Zhenyu
AU - Wang, Zhouguang
AU - Warnes, Gary
AU - Warnsmann, Verena
AU - Watada, Hirotaka
AU - Watanabe, Eizo
AU - Watchon, Maxinne
AU - Wawrzyńska, Anna
AU - Weaver, Timothy E.
AU - Wegrzyn, Grzegorz
AU - Wehman, Ann M.
AU - Wei, Huafeng
AU - Wei, Lei
AU - Wei, Taotao
AU - Wei, Yongjie
AU - Weiergräber, Oliver H.
AU - Weihl, Conrad C.
AU - Weindl, Günther
AU - Weiskirchen, Ralf
AU - Wells, Alan
AU - Wen, Runxia H.
AU - Wen, Xin
AU - Werner, Antonia
AU - Weykopf, Beatrice
AU - Wheatley, Sally P.
AU - Whitton, J. Lindsay
AU - Whitworth, Alexander J.
AU - Wiktorska, Katarzyna
AU - Wildenberg, Manon E.
AU - Wileman, Tom
AU - Wilkinson, Simon
AU - Willbold, Dieter
AU - Williams, Brett
AU - Williams, Robin S.B.
AU - Williams, Roger L.
AU - Williamson, Peter R.
AU - Wilson, Richard A.
AU - Winner, Beate
AU - Winsor, Nathaniel J.
AU - Witkin, Steven S.
AU - Wodrich, Harald
AU - Woehlbier, Ute
AU - Wollert, Thomas
AU - Wong, Esther
AU - Wong, Jack Ho
AU - Wong, Richard W.
AU - Wong, Vincent Kam Wai
AU - Wong, W. Wei Lynn
AU - Wu, An Guo
AU - Wu, Chengbiao
AU - Wu, Jian
AU - Wu, Junfang
AU - Wu, Kenneth K.
AU - Wu, Min
AU - Wu, Shan Ying
AU - Wu, Shengzhou
AU - Wu, Shu Yan
AU - Wu, Shufang
AU - Wu, William K.K.
AU - Wu, Xiaohong
AU - Wu, Xiaoqing
AU - Wu, Yao Wen
AU - Wu, Yihua
AU - Xavier, Ramnik J.
AU - Xia, Hongguang
AU - Xia, Lixin
AU - Xia, Zhengyuan
AU - Xiang, Ge
AU - Xiang, Jin
AU - Xiang, Mingliang
AU - Xiang, Wei
AU - Xiao, Bin
AU - Xiao, Guozhi
AU - Xiao, Hengyi
AU - Xiao, Hong Tao
AU - Xiao, Jian
AU - Xiao, Lan
AU - Xiao, Shi
AU - Xiao, Yin
AU - Xie, Baoming
AU - Xie, Chuan Ming
AU - Xie, Min
AU - Xie, Yuxiang
AU - Xie, Zhiping
AU - Xie, Zhonglin
AU - Xilouri, Maria
AU - Xu, Congfeng
AU - Xu, En
AU - Xu, Haoxing
AU - Xu, Jing
AU - Xu, Jin Rong
AU - Xu, Liang
AU - Xu, Wen Wen
AU - Xu, Xiulong
AU - Xue, Yu
AU - Yakhine-Diop, Sokhna M.S.
AU - Yamaguchi, Masamitsu
AU - Yamaguchi, Osamu
AU - Yamamoto, Ai
AU - Yamashina, Shunhei
AU - Yan, Shengmin
AU - Yan, Shian Jang
AU - Yan, Zhen
AU - Yanagi, Yasuo
AU - Yang, Chuanbin
AU - Yang, Dun Sheng
AU - Yang, Huan
AU - Yang, Huang Tian
AU - Yang, Hui
AU - Yang, Jin Ming
AU - Yang, Jing
AU - Yang, Jingyu
AU - Yang, Ling
AU - Yang, Liu
AU - Yang, Ming
AU - Yang, Pei Ming
AU - Yang, Qian
AU - Yang, Seungwon
AU - Yang, Shu
AU - Yang, Shun Fa
AU - Yang, Wannian
AU - Yang, Wei Yuan
AU - Yang, Xiaoyong
AU - Yang, Xuesong
AU - Yang, Yi
AU - Yang, Ying
AU - Yao, Honghong
AU - Yao, Shenggen
AU - Yao, Xiaoqiang
AU - Yao, Yong Gang
AU - Yao, Yong Ming
AU - Yasui, Takahiro
AU - Yazdankhah, Meysam
AU - Yen, Paul M.
AU - Yi, Cong
AU - Yin, Xiao Ming
AU - Yin, Yanhai
AU - Yin, Zhangyuan
AU - Yin, Ziyi
AU - Ying, Meidan
AU - Ying, Zheng
AU - Yip, Calvin K.
AU - Yiu, Stephanie Pei Tung
AU - Yoo, Young H.
AU - Yoshida, Kiyotsugu
AU - Yoshii, Saori R.
AU - Yoshimori, Tamotsu
AU - Yousefi, Bahman
AU - Yu, Boxuan
AU - Yu, Haiyang
AU - Yu, Jun
AU - Yu, Jun
AU - Yu, Li
AU - Yu, Ming Lung
AU - Yu, Seong Woon
AU - Yu, Victor C.
AU - Yu, W. Haung
AU - Yu, Zhengping
AU - Yu, Zhou
AU - Yuan, Junying
AU - Yuan, Ling Qing
AU - Yuan, Shilin
AU - Yuan, Shyng Shiou F.
AU - Yuan, Yanggang
AU - Yuan, Zengqiang
AU - Yue, Jianbo
AU - Yue, Zhenyu
AU - Yun, Jeanho
AU - Yung, Raymond L.
AU - Zacks, David N.
AU - Zaffagnini, Gabriele
AU - Zambelli, Vanessa O.
AU - Zanella, Isabella
AU - Zang, Qun S.
AU - Zanivan, Sara
AU - Zappavigna, Silvia
AU - Zaragoza, Pilar
AU - Zarbalis, Konstantinos S.
AU - Zarebkohan, Amir
AU - Zarrouk, Amira
AU - Zeitlin, Scott O.
AU - Zeng, Jialiu
AU - Zeng, Ju Deng
AU - Žerovnik, Eva
AU - Zhan, Lixuan
AU - Zhang, Bin
AU - Zhang, Donna D.
AU - Zhang, Hanlin
AU - Zhang, Hong
AU - Zhang, Hong
AU - Zhang, Honghe
AU - Zhang, Huafeng
AU - Zhang, Huaye
AU - Zhang, Hui
AU - Zhang, Hui Ling
AU - Zhang, Jianbin
AU - Zhang, Jianhua
AU - Zhang, Jing Pu
AU - Zhang, Kalin Y.B.
AU - Zhang, Leshuai W.
AU - Zhang, Lin
AU - Zhang, Lisheng
AU - Zhang, Lu
AU - Zhang, Luoying
AU - Zhang, Menghuan
AU - Zhang, Peng
AU - Zhang, Sheng
AU - Zhang, Wei
AU - Zhang, Xiangnan
AU - Zhang, Xiao Wei
AU - Zhang, Xiaolei
AU - Zhang, Xiaoyan
AU - Zhang, Xin
AU - Zhang, Xinxin
AU - Zhang, Xu Dong
AU - Zhang, Yang
AU - Zhang, Yanjin
AU - Zhang, Yi
AU - Zhang, Ying Dong
AU - Zhang, Yingmei
AU - Zhang, Yuan Yuan
AU - Zhang, Yuchen
AU - Zhang, Zhe
AU - Zhang, Zhengguang
AU - Zhang, Zhibing
AU - Zhang, Zhihai
AU - Zhang, Zhiyong
AU - Zhang, Zili
AU - Zhao, Haobin
AU - Zhao, Lei
AU - Zhao, Shuang
AU - Zhao, Tongbiao
AU - Zhao, Xiao Fan
AU - Zhao, Ying
AU - Zhao, Yongchao
AU - Zhao, Yongliang
AU - Zhao, Yuting
AU - Zheng, Guoping
AU - Zheng, Kai
AU - Zheng, Ling
AU - Zheng, Shizhong
AU - Zheng, Xi Long
AU - Zheng, Yi
AU - Zheng, Zu Guo
AU - Zhivotovsky, Boris
AU - Zhong, Qing
AU - Zhou, Ao
AU - Zhou, Ben
AU - Zhou, Cefan
AU - Zhou, Gang
AU - Zhou, Hao
AU - Zhou, Hong
AU - Zhou, Hongbo
AU - Zhou, Jie
AU - Zhou, Jing
AU - Zhou, Jing
AU - Zhou, Jiyong
AU - Zhou, Kailiang
AU - Zhou, Rongjia
AU - Zhou, Xu Jie
AU - Zhou, Yanshuang
AU - Zhou, Yinghong
AU - Zhou, Yubin
AU - Zhou, Zheng Yu
AU - Zhou, Zhou
AU - Zhu, Binglin
AU - Zhu, Changlian
AU - Zhu, Guo Qing
AU - Zhu, Haining
AU - Zhu, Hongxin
AU - Zhu, Hua
AU - Zhu, Wei Guo
AU - Zhu, Yanping
AU - Zhu, Yushan
AU - Zhuang, Haixia
AU - Zhuang, Xiaohong
AU - Zientara-Rytter, Katarzyna
AU - Zimmermann, Christine M.
AU - Ziviani, Elena
AU - Zoladek, Teresa
AU - Zong, Wei Xing
AU - Zorov, Dmitry B.
AU - Zorzano, Antonio
AU - Zou, Weiping
AU - Zou, Zhen
AU - Zou, Zhengzhi
AU - Zuryn, Steven
AU - Zwerschke, Werner
AU - Brand-Saberi, Beate
AU - Dong, X. Charlie
AU - Kenchappa, Chandra Shekar
AU - Li, Zuguo
AU - Lin, Yong
AU - Oshima, Shigeru
AU - Rong, Yueguang
AU - Sluimer, Judith C.
AU - Stallings, Christina L.
AU - Tong, Chun Kit
ID - 9298
IS - 1
JF - Autophagy
SN - 1554-8627
TI - Guidelines for the use and interpretation of assays for monitoring autophagy (4th edition)
VL - 17
ER -
TY - JOUR
AB - Growth regulation tailors development in plants to their environment. A prominent example of this is the response to gravity, in which shoots bend up and roots bend down1. This paradox is based on opposite effects of the phytohormone auxin, which promotes cell expansion in shoots while inhibiting it in roots via a yet unknown cellular mechanism2. Here, by combining microfluidics, live imaging, genetic engineering and phosphoproteomics in Arabidopsis thaliana, we advance understanding of how auxin inhibits root growth. We show that auxin activates two distinct, antagonistically acting signalling pathways that converge on rapid regulation of apoplastic pH, a causative determinant of growth. Cell surface-based TRANSMEMBRANE KINASE1 (TMK1) interacts with and mediates phosphorylation and activation of plasma membrane H+-ATPases for apoplast acidification, while intracellular canonical auxin signalling promotes net cellular H+ influx, causing apoplast alkalinization. Simultaneous activation of these two counteracting mechanisms poises roots for rapid, fine-tuned growth modulation in navigating complex soil environments.
AU - Li, Lanxin
AU - Verstraeten, Inge
AU - Roosjen, Mark
AU - Takahashi, Koji
AU - Rodriguez Solovey, Lesia
AU - Merrin, Jack
AU - Chen, Jian
AU - Shabala, Lana
AU - Smet, Wouter
AU - Ren, Hong
AU - Vanneste, Steffen
AU - Shabala, Sergey
AU - De Rybel, Bert
AU - Weijers, Dolf
AU - Kinoshita, Toshinori
AU - Gray, William M.
AU - Friml, Jiří
ID - 10223
IS - 7884
JF - Nature
KW - Multidisciplinary
SN - 00280836
TI - Cell surface and intracellular auxin signalling for H+ fluxes in root growth
VL - 599
ER -
TY - JOUR
AB - Transposable elements exist widely throughout plant genomes and play important roles in plant evolution. Auxin is an important regulator that is traditionally associated with root development and drought stress adaptation. The DEEPER ROOTING 1 (DRO1) gene is a key component of rice drought avoidance. Here, we identified a transposon that acts as an autonomous auxin‐responsive promoter and its presence at specific genome positions conveys physiological adaptations related to drought avoidance. Rice varieties with high and auxin‐mediated transcription of DRO1 in the root tip show deeper and longer root phenotypes and are thus better adapted to drought. The INDITTO2 transposon contains an auxin response element and displays auxin‐responsive promoter activity; it is thus able to convey auxin regulation of transcription to genes in its proximity. In the rice Acuce, which displays DRO1‐mediated drought adaptation, the INDITTO2 transposon was found to be inserted at the promoter region of the DRO1 locus. Transgenesis‐based insertion of the INDITTO2 transposon into the DRO1 promoter of the non‐adapted rice variety Nipponbare was sufficient to promote its drought avoidance. Our data identify an example of how transposons can act as promoters and convey hormonal regulation to nearby loci, improving plant fitness in response to different abiotic stresses.
AU - Zhao, Y
AU - Wu, L
AU - Fu, Q
AU - Wang, D
AU - Li, J
AU - Yao, B
AU - Yu, S
AU - Jiang, L
AU - Qian, J
AU - Zhou, X
AU - Han, L
AU - Zhao, S
AU - Ma, C
AU - Zhang, Y
AU - Luo, C
AU - Dong, Q
AU - Li, S
AU - Zhang, L
AU - Jiang, X
AU - Li, Y
AU - Luo, H
AU - Li, K
AU - Yang, J
AU - Luo, Q
AU - Li, L
AU - Peng, S
AU - Huang, H
AU - Zuo, Z
AU - Liu, C
AU - Wang, L
AU - Li, C
AU - He, X
AU - Friml, Jiří
AU - Du, Y
ID - 9189
IS - 6
JF - Plant, Cell & Environment
SN - 0140-7791
TI - INDITTO2 transposon conveys auxin-mediated DRO1 transcription for rice drought avoidance
VL - 44
ER -
TY - JOUR
AB - Clathrin-mediated endocytosis is the major route of entry of cargos into cells and thus underpins many physiological processes. During endocytosis, an area of flat membrane is remodeled by proteins to create a spherical vesicle against intracellular forces. The protein machinery which mediates this membrane bending in plants is unknown. However, it is known that plant endocytosis is actin independent, thus indicating that plants utilize a unique mechanism to mediate membrane bending against high-turgor pressure compared to other model systems. Here, we investigate the TPLATE complex, a plant-specific endocytosis protein complex. It has been thought to function as a classical adaptor functioning underneath the clathrin coat. However, by using biochemical and advanced live microscopy approaches, we found that TPLATE is peripherally associated with clathrin-coated vesicles and localizes at the rim of endocytosis events. As this localization is more fitting to the protein machinery involved in membrane bending during endocytosis, we examined cells in which the TPLATE complex was disrupted and found that the clathrin structures present as flat patches. This suggests a requirement of the TPLATE complex for membrane bending during plant clathrin–mediated endocytosis. Next, we used in vitro biophysical assays to confirm that the TPLATE complex possesses protein domains with intrinsic membrane remodeling activity. These results redefine the role of the TPLATE complex and implicate it as a key component of the evolutionarily distinct plant endocytosis mechanism, which mediates endocytic membrane bending against the high-turgor pressure in plant cells.
AU - Johnson, Alexander J
AU - Dahhan, Dana A
AU - Gnyliukh, Nataliia
AU - Kaufmann, Walter
AU - Zheden, Vanessa
AU - Costanzo, Tommaso
AU - Mahou, Pierre
AU - Hrtyan, Mónika
AU - Wang, Jie
AU - Aguilera Servin, Juan L
AU - van Damme, Daniël
AU - Beaurepaire, Emmanuel
AU - Loose, Martin
AU - Bednarek, Sebastian Y
AU - Friml, Jiří
ID - 9887
IS - 51
JF - Proceedings of the National Academy of Sciences
TI - The TPLATE complex mediates membrane bending during plant clathrin-mediated endocytosis
VL - 118
ER -
TY - GEN
AB - Raw data generated from the publication - The TPLATE complex mediates membrane bending during plant clathrin-mediated endocytosis by Johnson et al., 2021 In PNAS
AU - Johnson, Alexander J
ID - 14988
TI - Raw data from Johnson et al, PNAS, 2021
ER -
TY - THES
AB - Blood – this is what animals use to heal wounds fast and efficient. Plants do not have blood circulation and their cells cannot move. However, plants have evolved remarkable capacities to regenerate tissues and organs preventing further damage. In my PhD research, I studied the wound healing in the Arabidopsis root. I used a UV laser to ablate single cells in the root tip and observed the consequent wound healing. Interestingly, the inner adjacent cells induced a
division plane switch and subsequently adopted the cell type of the killed cell to replace it. We termed this form of wound healing “restorative divisions”. This initial observation triggered the questions of my PhD studies: How and why do cells orient their division planes, how do they feel the wound and why does this happen only in inner adjacent cells.
For answering these questions, I used a quite simple experimental setup: 5 day - old seedlings were stained with propidium iodide to visualize cell walls and dead cells; ablation was carried out using a special laser cutter and a confocal microscope. Adaptation of the novel vertical microscope system made it possible to observe wounds in real time. This revealed that restorative divisions occur at increased frequency compared to normal divisions. Additionally,
the major plant hormone auxin accumulates in wound adjacent cells and drives the expression of the wound-stress responsive transcription factor ERF115. Using this as a marker gene for wound responses, we found that an important part of wound signalling is the sensing of the collapse of the ablated cell. The collapse causes a radical pressure drop, which results in strong tissue deformations. These deformations manifest in an invasion of the now free spot specifically by the inner adjacent cells within seconds, probably because of higher pressure of the inner tissues. Long-term imaging revealed that those deformed cells continuously expand towards the wound hole and that this is crucial for the restorative division. These wound-expanding cells exhibit an abnormal, biphasic polarity of microtubule arrays
before the division. Experiments inhibiting cell expansion suggest that it is the biphasic stretching that induces those MT arrays. Adapting the micromanipulator aspiration system from animal scientists at our institute confirmed the hypothesis that stretching influences microtubule stability. In conclusion, this shows that microtubules react to tissue deformation
and this facilitates the observed division plane switch. This puts mechanical cues and tensions at the most prominent position for explaining the growth and wound healing properties of plants. Hence, it shines light onto the importance of understanding mechanical signal transduction.
AU - Hörmayer, Lukas
ID - 9992
SN - 2663-337X
TI - Wound healing in the Arabidopsis root meristem
ER -
TY - JOUR
AB - Availability of the essential macronutrient nitrogen in soil plays a critical role in plant growth, development, and impacts agricultural productivity. Plants have evolved different strategies for sensing and responding to heterogeneous nitrogen distribution. Modulation of root system architecture, including primary root growth and branching, is among the most essential plant adaptions to ensure adequate nitrogen acquisition. However, the immediate molecular pathways coordinating the adjustment of root growth in response to distinct nitrogen sources, such as nitrate or ammonium, are poorly understood. Here, we show that growth as manifested by cell division and elongation is synchronized by coordinated auxin flux between two adjacent outer tissue layers of the root. This coordination is achieved by nitrate‐dependent dephosphorylation of the PIN2 auxin efflux carrier at a previously uncharacterized phosphorylation site, leading to subsequent PIN2 lateralization and thereby regulating auxin flow between adjacent tissues. A dynamic computer model based on our experimental data successfully recapitulates experimental observations. Our study provides mechanistic insights broadening our understanding of root growth mechanisms in dynamic environments.
AU - Ötvös, Krisztina
AU - Marconi, Marco
AU - Vega, Andrea
AU - O’Brien, Jose
AU - Johnson, Alexander J
AU - Abualia, Rashed
AU - Antonielli, Livio
AU - Montesinos López, Juan C
AU - Zhang, Yuzhou
AU - Tan, Shutang
AU - Cuesta, Candela
AU - Artner, Christina
AU - Bouguyon, Eleonore
AU - Gojon, Alain
AU - Friml, Jiří
AU - Gutiérrez, Rodrigo A.
AU - Wabnik, Krzysztof T
AU - Benková, Eva
ID - 9010
IS - 3
JF - EMBO Journal
SN - 02614189
TI - Modulation of plant root growth by nitrogen source-defined regulation of polar auxin transport
VL - 40
ER -
TY - JOUR
AB - Auxin is a major plant growth regulator, but current models on auxin perception and signaling cannot explain the whole plethora of auxin effects, in particular those associated with rapid responses. A possible candidate for a component of additional auxin perception mechanisms is the AUXIN BINDING PROTEIN 1 (ABP1), whose function in planta remains unclear.
Here we combined expression analysis with gain- and loss-of-function approaches to analyze the role of ABP1 in plant development. ABP1 shows a broad expression largely overlapping with, but not regulated by, transcriptional auxin response activity. Furthermore, ABP1 activity is not essential for the transcriptional auxin signaling. Genetic in planta analysis revealed that abp1 loss-of-function mutants show largely normal development with minor defects in bolting. On the other hand, ABP1 gain-of-function alleles show a broad range of growth and developmental defects, including root and hypocotyl growth and bending, lateral root and leaf development, bolting, as well as response to heat stress. At the cellular level, ABP1 gain-of-function leads to impaired auxin effect on PIN polar distribution and affects BFA-sensitive PIN intracellular aggregation.
The gain-of-function analysis suggests a broad, but still mechanistically unclear involvement of ABP1 in plant development, possibly masked in abp1 loss-of-function mutants by a functional redundancy.
AU - Gelová, Zuzana
AU - Gallei, Michelle C
AU - Pernisová, Markéta
AU - Brunoud, Géraldine
AU - Zhang, Xixi
AU - Glanc, Matous
AU - Li, Lanxin
AU - Michalko, Jaroslav
AU - Pavlovicova, Zlata
AU - Verstraeten, Inge
AU - Han, Huibin
AU - Hajny, Jakub
AU - Hauschild, Robert
AU - Čovanová, Milada
AU - Zwiewka, Marta
AU - Hörmayer, Lukas
AU - Fendrych, Matyas
AU - Xu, Tongda
AU - Vernoux, Teva
AU - Friml, Jiří
ID - 8931
JF - Plant Science
KW - Agronomy and Crop Science
KW - Plant Science
KW - Genetics
KW - General Medicine
SN - 0168-9452
TI - Developmental roles of auxin binding protein 1 in Arabidopsis thaliana
VL - 303
ER -
TY - JOUR
AB - The phytohormone auxin and its directional transport through tissues are intensively studied. However, a mechanistic understanding of auxin-mediated feedback on endocytosis and polar distribution of PIN auxin transporters remains limited due to contradictory observations and interpretations. Here, we used state-of-the-art methods to reexamine the
auxin effects on PIN endocytic trafficking. We used high auxin concentrations or longer treatments versus lower concentrations and shorter treatments of natural (IAA) and synthetic (NAA) auxins to distinguish between specific and nonspecific effects. Longer treatments of both auxins interfere with Brefeldin A-mediated intracellular PIN2 accumulation and also with general aggregation of endomembrane compartments. NAA treatment decreased the internalization of the endocytic tracer dye, FM4-64; however, NAA treatment also affected the number, distribution, and compartment identity of the early endosome/trans-Golgi network (EE/TGN), rendering the FM4-64 endocytic assays at high NAA concentrations unreliable. To circumvent these nonspecific effects of NAA and IAA affecting the endomembrane system, we opted for alternative approaches visualizing the endocytic events directly at the plasma membrane (PM). Using Total Internal Reflection Fluorescence (TIRF) microscopy, we saw no significant effects of IAA or NAA treatments on the incidence and dynamics of clathrin foci, implying that these treatments do not affect the overall endocytosis rate. However, both NAA and IAA at low concentrations rapidly and specifically promoted endocytosis of photo-converted PIN2 from the PM. These analyses identify a specific effect of NAA and IAA on PIN2 endocytosis, thus contributing to its
polarity maintenance and furthermore illustrate that high auxin levels have nonspecific effects on trafficking and endomembrane compartments.
AU - Narasimhan, Madhumitha
AU - Gallei, Michelle C
AU - Tan, Shutang
AU - Johnson, Alexander J
AU - Verstraeten, Inge
AU - Li, Lanxin
AU - Rodriguez Solovey, Lesia
AU - Han, Huibin
AU - Himschoot, E
AU - Wang, R
AU - Vanneste, S
AU - Sánchez-Simarro, J
AU - Aniento, F
AU - Adamowski, Maciek
AU - Friml, Jiří
ID - 9287
IS - 2
JF - Plant Physiology
SN - 0032-0889
TI - Systematic analysis of specific and nonspecific auxin effects on endocytosis and trafficking
VL - 186
ER -
TY - THES
AB - Plant motions occur across a wide spectrum of timescales, ranging from seed dispersal through bursting (milliseconds) and stomatal opening (minutes) to long-term adaptation of gross architecture. Relatively fast motions include water-driven growth as exemplified by root cell expansion under abiotic/biotic stresses or during gravitropism. A showcase is a root growth inhibition in 30 seconds triggered by the phytohormone auxin. However, the cellular and molecular mechanisms are still largely unknown. This thesis covers the studies about this topic as follows. By taking advantage of microfluidics combined with live imaging, pharmaceutical tools, and transgenic lines, we examined the kinetics of and causal relationship among various auxininduced rapid cellular changes in root growth, apoplastic pH, cytosolic Ca2+, cortical microtubule (CMT) orientation, and vacuolar morphology. We revealed that CMT reorientation and vacuolar constriction are the consequence of growth itself instead of responding directly to auxin. In contrast, auxin induces apoplast alkalinization to rapidly inhibit root growth in 30 seconds. This auxin-triggered apoplast alkalinization results from rapid H+- influx that is contributed by Ca2+ inward channel CYCLIC NUCLEOTIDE-GATED CHANNEL 14 (CNGC14)-dependent Ca2+ signaling. To dissect which auxin signaling mediates the rapid apoplast alkalinization, we
combined microfluidics and genetic engineering to verify that TIR1/AFB receptors conduct a non-transcriptional regulation on Ca2+ and H+ -influx. This non-canonical pathway is mostly mediated by the cytosolic portion of TIR1/AFB. On the other hand, we uncovered, using biochemical and phospho-proteomic analysis, that auxin cell surface signaling component TRANSMEMBRANE KINASE 1 (TMK1) plays a negative role during auxin-trigger apoplast
alkalinization and root growth inhibition through directly activating PM H+ -ATPases. Therefore, we discovered that PM H+ -ATPases counteract instead of mediate the auxintriggered rapid H+ -influx, and that TIR1/AFB and TMK1 regulate root growth antagonistically. This opposite effect of TIR1/AFB and TMK1 is consistent during auxin-induced hypocotyl elongation, leading us to explore the relation of two signaling pathways. Assisted with biochemistry and fluorescent imaging, we verified for the first time that TIR1/AFB and TMK1 can interact with each other. The ability of TIR1/AFB binding to membrane lipid provides a basis for the interaction of plasma membrane- and cytosol-localized proteins.
Besides, transgenic analysis combined with genetic engineering and biochemistry showed that vi
they do function in the same pathway. Particularly, auxin-induced TMK1 increase is TIR1/AFB dependent, suggesting TIR1/AFB regulation on TMK1. Conversely, TMK1 also regulates TIR1/AFB protein levels and thus auxin canonical signaling. To follow the study of rapid growth regulation, we analyzed another rapid growth regulator, signaling peptide RALF1. We showed that RALF1 also triggers a rapid and reversible growth inhibition caused by H + influx, highly resembling but not dependent on auxin. Besides, RALF1 promotes auxin biosynthesis by increasing expression of auxin biosynthesis enzyme YUCCAs and thus induces auxin signaling in ca. 1 hour, contributing to the sustained RALF1-triggered growth inhibition. These studies collectively contribute to understanding rapid regulation on plant cell
growth, novel auxin signaling pathway as well as auxin-peptide crosstalk.
AU - Li, Lanxin
ID - 10083
SN - 2663-337X
TI - Rapid cell growth regulation in Arabidopsis
ER -
TY - JOUR
AB - Auxin plays a dual role in growth regulation and, depending on the tissue and concentration of the hormone, it can either promote or inhibit division and expansion processes in plants. Recent studies have revealed that, beyond transcriptional reprogramming, alternative auxincontrolled mechanisms regulate root growth. Here, we explored the impact of different concentrations of the synthetic auxin NAA that establish growth-promoting and -repressing conditions on the root tip proteome and phosphoproteome, generating a unique resource. From the phosphoproteome data, we pinpointed (novel) growth regulators, such as the RALF34-THE1 module. Our results, together with previously published studies, suggest that auxin, H+-ATPases, cell wall modifications and cell wall sensing receptor-like kinases are tightly embedded in a pathway regulating cell elongation. Furthermore, our study assigned a novel role to MKK2 as a regulator of primary root growth and a (potential) regulator of auxin biosynthesis and signalling, and suggests the importance of the MKK2
Thr31 phosphorylation site for growth regulation in the Arabidopsis root tip.
AU - Nikonorova, N
AU - Murphy, E
AU - Fonseca de Lima, CF
AU - Zhu, S
AU - van de Cotte, B
AU - Vu, LD
AU - Balcerowicz, D
AU - Li, Lanxin
AU - Kong, X
AU - De Rop, G
AU - Beeckman, T
AU - Friml, Jiří
AU - Vissenberg, K
AU - Morris, PC
AU - Ding, Z
AU - De Smet, I
ID - 10015
JF - Cells
KW - primary root
KW - (phospho)proteomics
KW - auxin
KW - (receptor) kinase
SN - 2073-4409
TI - The Arabidopsis root tip (phospho)proteomes at growth-promoting versus growth-repressing conditions reveal novel root growth regulators
VL - 10
ER -
TY - GEN
AB - Growth regulation tailors plant development to its environment. A showcase is response to gravity, where shoots bend up and roots down1. This paradox is based on opposite effects of the phytohormone auxin, which promotes cell expansion in shoots, while inhibiting it in roots via a yet unknown cellular mechanism2. Here, by combining microfluidics, live imaging, genetic engineering and phospho-proteomics in Arabidopsis thaliana, we advance our understanding how auxin inhibits root growth. We show that auxin activates two distinct, antagonistically acting signalling pathways that converge on the rapid regulation of the apoplastic pH, a causative growth determinant. Cell surface-based TRANSMEMBRANE KINASE1 (TMK1) interacts with and mediates phosphorylation and activation of plasma membrane H+-ATPases for apoplast acidification, while intracellular canonical auxin signalling promotes net cellular H+-influx, causing apoplast alkalinisation. The simultaneous activation of these two counteracting mechanisms poises the root for a rapid, fine-tuned growth modulation while navigating complex soil environment.
AU - Li, Lanxin
AU - Verstraeten, Inge
AU - Roosjen, Mark
AU - Takahashi, Koji
AU - Rodriguez Solovey, Lesia
AU - Merrin, Jack
AU - Chen, Jian
AU - Shabala, Lana
AU - Smet, Wouter
AU - Ren, Hong
AU - Vanneste, Steffen
AU - Shabala, Sergey
AU - De Rybel, Bert
AU - Weijers, Dolf
AU - Kinoshita, Toshinori
AU - Gray, William M.
AU - Friml, Jiří
ID - 10095
SN - 2693-5015
T2 - Research Square
TI - Cell surface and intracellular auxin signalling for H+-fluxes in root growth
ER -
TY - GEN
AB - Plasmodesmata (PD) are crucial structures for intercellular communication in multicellular plants with remorins being their crucial plant-specific structural and functional constituents. The PD biogenesis is an intriguing but poorly understood process. By expressing an Arabidopsis remorin protein in mammalian cells, we have reconstituted a PD-like filamentous structure, termed remorin filament (RF), connecting neighboring cells physically and physiologically. Notably, RFs are capable of transporting macromolecules intercellularly, in a way similar to plant PD. With further super-resolution microscopic analysis and biochemical characterization, we found that RFs are also composed of actin filaments, forming the core skeleton structure, aligned with the remorin protein. This unique heterologous filamentous structure might explain the molecular mechanism for remorin function as well as PD construction. Furthermore, remorin protein exhibits a specific distribution manner in the plasma membrane in mammalian cells, representing a lipid nanodomain, depending on its lipid modification status. Our studies not only provide crucial insights into the mechanism of PD biogenesis, but also uncovers unsuspected fundamental mechanistic and evolutionary links between intercellular communication systems of plants and animals.
AU - Wei, Zhuang
AU - Tan, Shutang
AU - Liu, Tao
AU - Wu, Yuan
AU - Lei, Ji-Gang
AU - Chen, ZhengJun
AU - Friml, Jiří
AU - Xue, Hong-Wei
AU - Liao, Kan
ID - 7601
T2 - bioRxiv
TI - Plasmodesmata-like intercellular connections by plant remorin in animal cells
ER -
TY - JOUR
AU - Zhang, Yuzhou
AU - Friml, Jiří
ID - 6997
IS - 3
JF - New Phytologist
SN - 0028-646x
TI - Auxin guides roots to avoid obstacles during gravitropic growth
VL - 225
ER -
TY - JOUR
AB - Plant root architecture dynamically adapts to various environmental conditions, such as salt‐containing soil. The phytohormone abscisic acid (ABA) is involved among others also in these developmental adaptations, but the underlying molecular mechanism remains elusive. Here, a novel branch of the ABA signaling pathway in Arabidopsis involving PYR/PYL/RCAR (abbreviated as PYLs) receptor‐protein phosphatase 2A (PP2A) complex that acts in parallel to the canonical PYLs‐protein phosphatase 2C (PP2C) mechanism is identified. The PYLs‐PP2A signaling modulates root gravitropism and lateral root formation through regulating phytohormone auxin transport. In optimal conditions, PYLs ABA receptor interacts with the catalytic subunits of PP2A, increasing their phosphatase activity and thus counteracting PINOID (PID) kinase‐mediated phosphorylation of PIN‐FORMED (PIN) auxin transporters. By contrast, in salt and osmotic stress conditions, ABA binds to PYLs, inhibiting the PP2A activity, which leads to increased PIN phosphorylation and consequently modulated directional auxin transport leading to adapted root architecture. This work reveals an adaptive mechanism that may flexibly adjust plant root growth to withstand saline and osmotic stresses. It occurs via the cross‐talk between the stress hormone ABA and the versatile developmental regulator auxin.
AU - Li, Yang
AU - Wang, Yaping
AU - Tan, Shutang
AU - Li, Zhen
AU - Yuan, Zhi
AU - Glanc, Matous
AU - Domjan, David
AU - Wang, Kai
AU - Xuan, Wei
AU - Guo, Yan
AU - Gong, Zhizhong
AU - Friml, Jiří
AU - Zhang, Jing
ID - 7204
IS - 3
JF - Advanced Science
TI - Root growth adaptation is mediated by PYLs ABA receptor-PP2A protein phosphatase complex
VL - 7
ER -
TY - JOUR
AB - The phytohormone auxin acts as an amazingly versatile coordinator of plant growth and development. With its morphogen-like properties, auxin controls sites and timing of differentiation and/or growth responses both, in quantitative and qualitative terms. Specificity in the auxin response depends largely on distinct modes of signal transmission, by which individual cells perceive and convert auxin signals into a remarkable diversity of responses. The best understood, or so-called canonical mechanism of auxin perception ultimately results in variable adjustments of the cellular transcriptome, via a short, nuclear signal transduction pathway. Additional findings that accumulated over decades implied that an additional, presumably, cell surface-based auxin perception mechanism mediates very rapid cellular responses and decisively contributes to the cell's overall hormonal response. Recent investigations into both, nuclear and cell surface auxin signalling challenged this assumed partition of roles for different auxin signalling pathways and revealed an unexpected complexity in transcriptional and non-transcriptional cellular responses mediated by auxin.
AU - Gallei, Michelle C
AU - Luschnig, Christian
AU - Friml, Jiří
ID - 7142
IS - 2
JF - Current Opinion in Plant Biology
SN - 1369-5266
TI - Auxin signalling in growth: Schrödinger's cat out of the bag
VL - 53
ER -
TY - JOUR
AB - Root system architecture (RSA), governed by the phytohormone auxin, endows plants with an adaptive advantage in particular environments. Using geographically representative arabidopsis (Arabidopsis thaliana) accessions as a resource for GWA mapping, Waidmann et al. and Ogura et al. recently identified two novel components involved in modulating auxin-mediated RSA and conferring plant fitness in particular habitats.
AU - Xiao, Guanghui
AU - Zhang, Yuzhou
ID - 7219
IS - 2
JF - Trends in Plant Science
SN - 13601385
TI - Adaptive growth: Shaping auxin-mediated root system architecture
VL - 25
ER -
TY - JOUR
AB - The flexible development of plants is characterized by a high capacity for post-embryonic organ formation and tissue regeneration, processes, which require tightly regulated intercellular communication and coordinated tissue (re-)polarization. The phytohormone auxin, the main driver for these processes, is able to establish polarized auxin transport channels, which are characterized by the expression and polar, subcellular localization of the PIN1 auxin transport proteins. These channels are demarcating the position of future vascular strands necessary for organ formation and tissue regeneration. Major progress has been made in the last years to understand how PINs can change their polarity in different contexts and thus guide auxin flow through the plant. However, it still remains elusive how auxin mediates the establishment of auxin conducting channels and the formation of vascular tissue and which cellular processes are involved. By the means of sophisticated regeneration experiments combined with local auxin applications in Arabidopsis thaliana inflorescence stems we show that (i) PIN subcellular dynamics, (ii) PIN internalization by clathrin-mediated trafficking and (iii) an intact actin cytoskeleton required for post-endocytic trafficking are indispensable for auxin channel formation, de novo vascular formation and vascular regeneration after wounding. These observations provide novel insights into cellular mechanism of coordinated tissue polarization during auxin canalization.
AU - Mazur, Ewa
AU - Gallei, Michelle C
AU - Adamowski, Maciek
AU - Han, Huibin
AU - Robert, Hélène S.
AU - Friml, Jiří
ID - 7465
IS - 4
JF - Plant Science
SN - 01689452
TI - Clathrin-mediated trafficking and PIN trafficking are required for auxin canalization and vascular tissue formation in Arabidopsis
VL - 293
ER -
TY - JOUR
AB - In plants, clathrin mediated endocytosis (CME) represents the major route for cargo internalisation from the cell surface. It has been assumed to operate in an evolutionary conserved manner as in yeast and animals. Here we report characterisation of ultrastructure, dynamics and mechanisms of plant CME as allowed by our advancement in electron microscopy and quantitative live imaging techniques. Arabidopsis CME appears to follow the constant curvature model and the bona fide CME population generates vesicles of a predominantly hexagonal-basket type; larger and with faster kinetics than in other models. Contrary to the existing paradigm, actin is dispensable for CME events at the plasma membrane but plays a unique role in collecting endocytic vesicles, sorting of internalised cargos and directional endosome movement that itself actively promote CME events. Internalized vesicles display a strongly delayed and sequential uncoating. These unique features highlight the independent evolution of the plant CME mechanism during the autonomous rise of multicellularity in eukaryotes.
AU - Narasimhan, Madhumitha
AU - Johnson, Alexander J
AU - Prizak, Roshan
AU - Kaufmann, Walter
AU - Tan, Shutang
AU - Casillas Perez, Barbara E
AU - Friml, Jiří
ID - 7490
JF - eLife
TI - Evolutionarily unique mechanistic framework of clathrin-mediated endocytosis in plants
VL - 9
ER -
TY - JOUR
AB - Endophytic fungi can be beneficial to plant growth. However, the molecular mechanisms underlying colonization of Acremonium spp. remain unclear. In this study, a novel endophytic Acremonium strain was isolated from the buds of Panax notoginseng and named Acremonium sp. D212. The Acremonium sp. D212 could colonize the roots of P. notoginseng, enhance the resistance of P. notoginseng to root rot disease, and promote root growth and saponin biosynthesis in P. notoginseng. Acremonium sp. D212 could secrete indole‐3‐acetic acid (IAA) and jasmonic acid (JA), and inoculation with the fungus increased the endogenous levels of IAA and JA in P. notoginseng. Colonization of the Acremonium sp. D212 in the roots of the rice line Nipponbare was dependent on the concentration of methyl jasmonate (MeJA) (2 to 15 μM) and 1‐naphthalenacetic acid (NAA) (10 to 20 μM). Moreover, the roots of the JA signalling‐defective coi1‐18 mutant were colonized by Acremonium sp. D212 to a lesser degree than those of the wild‐type Nipponbare and miR393b‐overexpressing lines, and the colonization was rescued by MeJA but not by NAA. It suggests that the cross‐talk between JA signalling and the auxin biosynthetic pathway plays a crucial role in the colonization of Acremonium sp. D212 in host plants.
AU - Han, L
AU - Zhou, X
AU - Zhao, Y
AU - Zhu, S
AU - Wu, L
AU - He, Y
AU - Ping, X
AU - Lu, X
AU - Huang, W
AU - Qian, J
AU - Zhang, L
AU - Jiang, X
AU - Zhu, D
AU - Luo, C
AU - Li, S
AU - Dong, Q
AU - Fu, Q
AU - Deng, K
AU - Wang, X
AU - Wang, L
AU - Peng, S
AU - Wu, J
AU - Li, W
AU - Friml, Jiří
AU - Zhu, Y
AU - He, X
AU - Du, Y
ID - 7497
IS - 9
JF - Journal of Integrative Plant Biology
SN - 1672-9072
TI - Colonization of endophyte Acremonium sp. D212 in Panax notoginseng and rice mediated by auxin and jasmonic acid
VL - 62
ER -
TY - JOUR
AB - In vitro propagation of the ornamentally interesting species Wikstroemia gemmata is limited by the recalcitrance to form adventitious roots. In this article, two strategies to improve the rooting capacity of in vitro microcuttings are presented. Firstly, the effect of exogenous auxin was evaluated in both light and dark cultivated stem segments and also the sucrose-content of the medium was varied in order to determine better rooting conditions. Secondly, different spectral lights were evaluated and the effect on shoot growth and root induction demonstrated that the exact spectral composition of light is important for successful in vitro growth and development of Wikstroemia gemmata. We show that exogenous auxin cannot compensate for the poor rooting under unfavorable light conditions. Adapting the culture conditions is therefore paramount for successful industrial propagation of Wikstroemia gemmata.
AU - Verstraeten, Inge
AU - Buyle, H.
AU - Werbrouck, S.
AU - Van Labeke, M.C.
AU - Geelen, D.
ID - 7540
IS - 1-2
JF - Israel Journal of Plant Sciences
SN - 0792-9978
TI - In vitro shoot growth and adventitious rooting of Wikstroemia gemmata depends on light quality
VL - 67
ER -
TY - JOUR
AB - Small RNAs (smRNA, 19–25 nucleotides long), which are transcribed by RNA polymerase II, regulate the expression of genes involved in a multitude of processes in eukaryotes. miRNA biogenesis and the proteins involved in the biogenesis pathway differ across plant and animal lineages. The major proteins constituting the biogenesis pathway, namely, the Dicers (DCL/DCR) and Argonautes (AGOs), have been extensively studied. However, the accessory proteins (DAWDLE (DDL), SERRATE (SE), and TOUGH (TGH)) of the pathway that differs across the two lineages remain largely uncharacterized. We present the first detailed report on the molecular evolution and divergence of these proteins across eukaryotes. Although DDL is present in eukaryotes and prokaryotes, SE and TGH appear to be specific to eukaryotes. The addition/deletion of specific domains and/or domain-specific sequence divergence in the three proteins points to the observed functional divergence of these proteins across the two lineages, which correlates with the differences in miRNA length across the two lineages. Our data enhance the current understanding of the structure–function relationship of these proteins and reveals previous unexplored crucial residues in the three proteins that can be used as a basis for further functional characterization. The data presented here on the number of miRNAs in crown eukaryotic lineages are consistent with the notion of the expansion of the number of miRNA-coding genes in animal and plant lineages correlating with organismal complexity. Whether this difference in functionally correlates with the diversification (or presence/absence) of the three proteins studied here or the miRNA signaling in the plant and animal lineages is unclear. Based on our results of the three proteins studied here and previously available data concerning the evolution of miRNA genes in the plant and animal lineages, we believe that miRNAs probably evolved once in the ancestor to crown eukaryotes and have diversified independently in the eukaryotes.
AU - Moturu, Taraka Ramji
AU - Sinha, Sansrity
AU - Salava, Hymavathi
AU - Thula, Sravankumar
AU - Nodzyński, Tomasz
AU - Vařeková, Radka Svobodová
AU - Friml, Jiří
AU - Simon, Sibu
ID - 7582
IS - 3
JF - Plants
TI - Molecular evolution and diversification of proteins involved in miRNA maturation pathway
VL - 9
ER -
TY - JOUR
AB - Directional intercellular transport of the phytohormone auxin mediated by PIN FORMED (PIN) efflux carriers plays essential roles in both coordinating patterning processes and integrating multiple external cues by rapidly redirecting auxin fluxes. Multilevel regulations of PIN activity under internal and external cues are complicated; however, the underlying molecular mechanism remains elusive. Here we demonstrate that 3’-Phosphoinositide-Dependent Protein Kinase1 (PDK1), which is conserved in plants and mammals, functions as a molecular hub integrating the upstream lipid signalling and the downstream substrate activity through phosphorylation. Genetic analysis uncovers that loss-of-function Arabidopsis mutant pdk1.1 pdk1.2 exhibits a plethora of abnormalities in organogenesis and growth, due to the defective PIN-dependent auxin transport. Further cellular and biochemical analyses reveal that PDK1 phosphorylates D6 Protein Kinase to facilitate its activity towards PIN proteins. Our studies establish a lipid-dependent phosphorylation cascade connecting membrane composition-based cellular signalling with plant growth and patterning by regulating morphogenetic auxin fluxes.
AU - Tan, Shutang
AU - Zhang, Xixi
AU - Kong, Wei
AU - Yang, Xiao-Li
AU - Molnar, Gergely
AU - Vondráková, Zuzana
AU - Filepová, Roberta
AU - Petrášek, Jan
AU - Friml, Jiří
AU - Xue, Hong-Wei
ID - 7600
JF - Nature Plants
TI - The lipid code-dependent phosphoswitch PDK1–D6PK activates PIN-mediated auxin efflux in Arabidopsis
VL - 6
ER -
TY - JOUR
AB - In plant cells, environmental stressors promote changes in connectivity between the cortical ER and the PM. Although this process is tightly regulated in space and time, the molecular signals and structural components mediating these changes in inter-organelle communication are only starting to be characterized. In this report, we confirm the presence of a putative tethering complex containing the synaptotagmins 1 and 5 (SYT1 and SYT5) and the Ca2+ and lipid binding protein 1 (CLB1/SYT7). This complex is enriched at ER-PM contact sites (EPCS), have slow responses to changes in extracellular Ca2+, and display severe cytoskeleton-dependent rearrangements in response to the trivalent lanthanum (La3+) and gadolinium (Gd3+) rare earth elements (REEs). Although REEs are generally used as non-selective cation channel blockers at the PM, here we show that the slow internalization of REEs into the cytosol underlies the activation of the Ca2+/Calmodulin intracellular signaling, the accumulation of phosphatidylinositol-4-phosphate (PI4P) at the PM, and the cytoskeleton-dependent rearrangement of the SYT1/SYT5 EPCS complexes. We propose that the observed EPCS rearrangements act as a slow adaptive response to sustained stress conditions, and that this process involves the accumulation of stress-specific phosphoinositides species at the PM.
AU - Lee, E
AU - Vila Nova Santana, B
AU - Samuels, E
AU - Benitez-Fuente, F
AU - Corsi, E
AU - Botella, MA
AU - Perez-Sancho, J
AU - Vanneste, S
AU - Friml, Jiří
AU - Macho, A
AU - Alves Azevedo, A
AU - Rosado, A
ID - 7646
IS - 14
JF - Journal of Experimental Botany
SN - 0022-0957
TI - Rare earth elements induce cytoskeleton-dependent and PI4P-associated rearrangement of SYT1/SYT5 ER-PM contact site complexes in Arabidopsis
VL - 71
ER -
TY - JOUR
AB - The agricultural green revolution spectacularly enhanced crop yield and lodging resistance with modified DELLA-mediated gibberellin signaling. However, this was achieved at the expense of reduced nitrogen-use efficiency (NUE). Recently, Wu et al. revealed novel gibberellin signaling that provides a blueprint for improving tillering and NUE in Green Revolution varieties (GRVs).
AU - Xue, Huidan
AU - Zhang, Yuzhou
AU - Xiao, Guanghui
ID - 7686
IS - 6
JF - Trends in Plant Science
SN - 1360-1385
TI - Neo-gibberellin signaling: Guiding the next generation of the green revolution
VL - 25
ER -
TY - JOUR
AB - Hormonal signalling in animals often involves direct transcription factor-hormone interactions that modulate gene expression. In contrast, plant hormone signalling is most commonly based on de-repression via the degradation of transcriptional repressors. Recently, we uncovered a non-canonical signalling mechanism for the plant hormone auxin whereby auxin directly affects the activity of the atypical auxin response factor (ARF), ETTIN towards target genes without the requirement for protein degradation. Here we show that ETTIN directly binds auxin, leading to dissociation from co-repressor proteins of the TOPLESS/TOPLESS-RELATED family followed by histone acetylation and induction of gene expression. This mechanism is reminiscent of animal hormone signalling as it affects the activity towards regulation of target genes and provides the first example of a DNA-bound hormone receptor in plants. Whilst auxin affects canonical ARFs indirectly by facilitating degradation of Aux/IAA repressors, direct ETTIN-auxin interactions allow switching between repressive and de-repressive chromatin states in an instantly-reversible manner.
AU - Kuhn, André
AU - Ramans Harborough, Sigurd
AU - McLaughlin, Heather M
AU - Natarajan, Bhavani
AU - Verstraeten, Inge
AU - Friml, Jiří
AU - Kepinski, Stefan
AU - Østergaard, Lars
ID - 7793
JF - eLife
SN - 2050-084X
TI - Direct ETTIN-auxin interaction controls chromatin states in gynoecium development
VL - 9
ER -
TY - JOUR
AB - Directional transport of the phytohormone auxin is a versatile, plant-specific mechanism regulating many aspects of plant development. The recently identified plant hormones, strigolactones (SLs), are implicated in many plant traits; among others, they modify the phenotypic output of PIN-FORMED (PIN) auxin transporters for fine-tuning of growth and developmental responses. Here, we show in pea and Arabidopsis that SLs target processes dependent on the canalization of auxin flow, which involves auxin feedback on PIN subcellular distribution. D14 receptor- and MAX2 F-box-mediated SL signaling inhibits the formation of auxin-conducting channels after wounding or from artificial auxin sources, during vasculature de novo formation and regeneration. At the cellular level, SLs interfere with auxin effects on PIN polar targeting, constitutive PIN trafficking as well as clathrin-mediated endocytosis. Our results identify a non-transcriptional mechanism of SL action, uncoupling auxin feedback on PIN polarity and trafficking, thereby regulating vascular tissue formation and regeneration.
AU - Zhang, J
AU - Mazur, E
AU - Balla, J
AU - Gallei, Michelle C
AU - Kalousek, P
AU - Medveďová, Z
AU - Li, Y
AU - Wang, Y
AU - Prat, Tomas
AU - Vasileva, Mina K
AU - Reinöhl, V
AU - Procházka, S
AU - Halouzka, R
AU - Tarkowski, P
AU - Luschnig, C
AU - Brewer, PB
AU - Friml, Jiří
ID - 8138
IS - 1
JF - Nature Communications
SN - 2041-1723
TI - Strigolactones inhibit auxin feedback on PIN-dependent auxin transport canalization
VL - 11
ER -
TY - JOUR
AU - He, Peng
AU - Zhang, Yuzhou
AU - Xiao, Guanghui
ID - 8271
IS - 9
JF - Molecular Plant
SN - 16742052
TI - Origin of a subgenome and genome evolution of allotetraploid cotton species
VL - 13
ER -
TY - JOUR
AB - Cytokinins are mobile multifunctional plant hormones with roles in development and stress resilience. Although their Histidine Kinase receptors are substantially localised to the endoplasmic reticulum, cellular sites of cytokinin perception and importance of spatially heterogeneous cytokinin distribution continue to be debated. Here we show that cytokinin perception by plasma membrane receptors is an effective additional path for cytokinin response. Readout from a Two Component Signalling cytokinin-specific reporter (TCSn::GFP) closely matches intracellular cytokinin content in roots, yet we also find cytokinins in extracellular fluid, potentially enabling action at the cell surface. Cytokinins covalently linked to beads that could not pass the plasma membrane increased expression of both TCSn::GFP and Cytokinin Response Factors. Super-resolution microscopy of GFP-labelled receptors and diminished TCSn::GFP response to immobilised cytokinins in cytokinin receptor mutants, further indicate that receptors can function at the cell surface. We argue that dual intracellular and surface locations may augment flexibility of cytokinin responses.
AU - Antoniadi, Ioanna
AU - Novák, Ondřej
AU - Gelová, Zuzana
AU - Johnson, Alexander J
AU - Plíhal, Ondřej
AU - Simerský, Radim
AU - Mik, Václav
AU - Vain, Thomas
AU - Mateo-Bonmatí, Eduardo
AU - Karady, Michal
AU - Pernisová, Markéta
AU - Plačková, Lenka
AU - Opassathian, Korawit
AU - Hejátko, Jan
AU - Robert, Stéphanie
AU - Friml, Jiří
AU - Doležal, Karel
AU - Ljung, Karin
AU - Turnbull, Colin
ID - 8337
JF - Nature Communications
TI - Cell-surface receptors enable perception of extracellular cytokinins
VL - 11
ER -
TY - JOUR
AB - Spontaneously arising channels that transport the phytohormone auxin provide positional cues for self-organizing aspects of plant development such as flexible vasculature regeneration or its patterning during leaf venation. The auxin canalization hypothesis proposes a feedback between auxin signaling and transport as the underlying mechanism, but molecular players await discovery. We identified part of the machinery that routes auxin transport. The auxin-regulated receptor CAMEL (Canalization-related Auxin-regulated Malectin-type RLK) together with CANAR (Canalization-related Receptor-like kinase) interact with and phosphorylate PIN auxin transporters. camel and canar mutants are impaired in PIN1 subcellular trafficking and auxin-mediated PIN polarization, which macroscopically manifests as defects in leaf venation and vasculature regeneration after wounding. The CAMEL-CANAR receptor complex is part of the auxin feedback that coordinates polarization of individual cells during auxin canalization.
AU - Hajny, Jakub
AU - Prat, Tomas
AU - Rydza, N
AU - Rodriguez Solovey, Lesia
AU - Tan, Shutang
AU - Verstraeten, Inge
AU - Domjan, David
AU - Mazur, E
AU - Smakowska-Luzan, E
AU - Smet, W
AU - Mor, E
AU - Nolf, J
AU - Yang, B
AU - Grunewald, W
AU - Molnar, Gergely
AU - Belkhadir, Y
AU - De Rybel, B
AU - Friml, Jiří
ID - 8721
IS - 6516
JF - Science
SN - 0036-8075
TI - Receptor kinase module targets PIN-dependent auxin transport during canalization
VL - 370
ER -
TY - JOUR
AB - Peptides derived from non-functional precursors play important roles in various developmental processes, but also in (a)biotic stress signaling. Our (phospho)proteome-wide analyses of C-terminally encoded peptide 5 (CEP5)-mediated changes revealed an impact on abiotic stress-related processes. Drought has a dramatic impact on plant growth, development and reproduction, and the plant hormone auxin plays a role in drought responses. Our genetic, physiological, biochemical and pharmacological results demonstrated that CEP5-mediated signaling is relevant for osmotic and drought stress tolerance in Arabidopsis, and that CEP5 specifically counteracts auxin effects. Specifically, we found that CEP5 signaling stabilizes AUX/IAA transcriptional repressors, suggesting the existence of a novel peptide-dependent control mechanism that tunes auxin signaling. These observations align with the recently described role of AUX/IAAs in stress tolerance and provide a novel role for CEP5 in osmotic and drought stress tolerance.
AU - Smith, S
AU - Zhu, S
AU - Joos, L
AU - Roberts, I
AU - Nikonorova, N
AU - Vu, LD
AU - Stes, E
AU - Cho, H
AU - Larrieu, A
AU - Xuan, W
AU - Goodall, B
AU - van de Cotte, B
AU - Waite, JM
AU - Rigal, A
AU - R Harborough, SR
AU - Persiau, G
AU - Vanneste, S
AU - Kirschner, GK
AU - Vandermarliere, E
AU - Martens, L
AU - Stahl, Y
AU - Audenaert, D
AU - Friml, Jiří
AU - Felix, G
AU - Simon, R
AU - Bennett, M
AU - Bishopp, A
AU - De Jaeger, G
AU - Ljung, K
AU - Kepinski, S
AU - Robert, S
AU - Nemhauser, J
AU - Hwang, I
AU - Gevaert, K
AU - Beeckman, T
AU - De Smet, I
ID - 7949
IS - 8
JF - Molecular & Cellular Proteomics
TI - The CEP5 peptide promotes abiotic stress tolerance, as revealed by quantitative proteomics, and attenuates the AUX/IAA equilibrium in Arabidopsis
VL - 19
ER -
TY - JOUR
AB - Cell polarity is a fundamental feature of all multicellular organisms. In plants, prominent cell polarity markers are PIN auxin transporters crucial for plant development. To identify novel components involved in cell polarity establishment and maintenance, we carried out a forward genetic screening with PIN2:PIN1-HA;pin2 Arabidopsis plants, which ectopically express predominantly basally localized PIN1 in the root epidermal cells leading to agravitropic root growth. From the screen, we identified the regulator of PIN polarity 12 (repp12) mutation, which restored gravitropic root growth and caused PIN1-HA polarity switch from basal to apical side of root epidermal cells. Complementation experiments established the repp12 causative mutation as an amino acid substitution in Aminophospholipid ATPase3 (ALA3), a phospholipid flippase with predicted function in vesicle formation. ala3 T-DNA mutants show defects in many auxin-regulated processes, in asymmetric auxin distribution and in PIN trafficking. Analysis of quintuple and sextuple mutants confirmed a crucial role of ALA proteins in regulating plant development and in PIN trafficking and polarity. Genetic and physical interaction studies revealed that ALA3 functions together with GNOM and BIG3 ARF GEFs. Taken together, our results identified ALA3 flippase as an important interactor and regulator of ARF GEF functioning in PIN polarity, trafficking and auxin-mediated development.
AU - Zhang, Xixi
AU - Adamowski, Maciek
AU - Marhavá, Petra
AU - Tan, Shutang
AU - Zhang, Yuzhou
AU - Rodriguez Solovey, Lesia
AU - Zwiewka, Marta
AU - Pukyšová, Vendula
AU - Sánchez, Adrià Sans
AU - Raxwal, Vivek Kumar
AU - Hardtke, Christian S.
AU - Nodzynski, Tomasz
AU - Friml, Jiří
ID - 7619
IS - 5
JF - The Plant Cell
SN - 1040-4651
TI - Arabidopsis flippases cooperate with ARF GTPase exchange factors to regulate the trafficking and polarity of PIN auxin transporters
VL - 32
ER -
TY - JOUR
AB - Clathrin-mediated endocytosis (CME) and its core endocytic machinery are evolutionarily conserved across all eukaryotes. In mammals, the heterotetrameric adaptor protein complex-2 (AP-2) sorts plasma membrane (PM) cargoes into vesicles through the recognition of motifs based on tyrosine or di-leucine in their cytoplasmic tails. However, in plants, very little is known on how PM proteins are sorted for CME and whether similar motifs are required. In Arabidopsis thaliana, the brassinosteroid (BR) receptor, BR INSENSITIVE1 (BRI1), undergoes endocytosis that depends on clathrin and AP-2. Here we demonstrate that BRI1 binds directly to the medium AP-2 subunit, AP2M. The cytoplasmic domain of BRI1 contains five putative canonical surface-exposed tyrosine-based endocytic motifs. The tyrosine-to-phenylalanine substitution in Y898KAI reduced BRI1 internalization without affecting its kinase activity. Consistently, plants carrying the BRI1Y898F mutation were hypersensitive to BRs. Our study demonstrates that AP-2-dependent internalization of PM proteins via the recognition of functional tyrosine motifs also operates in plants.
AU - Liu, D
AU - Kumar, R
AU - LAN, Claus
AU - Johnson, Alexander J
AU - Siao, W
AU - Vanhoutte, I
AU - Wang, P
AU - Bender, KW
AU - Yperman, K
AU - Martins, S
AU - Zhao, X
AU - Vert, G
AU - Van Damme, D
AU - Friml, Jiří
AU - Russinova, E
ID - 8607
IS - 11
JF - Plant Cell
SN - 1040-4651
TI - Endocytosis of BRASSINOSTEROID INSENSITIVE1 is partly driven by a canonical tyrosine-based Motif
VL - 32
ER -
TY - JOUR
AB - The TPLATE complex (TPC) is a key endocytic adaptor protein complex in plants. TPC in Arabidopsis (Arabidopsis thaliana) contains six evolutionarily conserved subunits and two plant-specific subunits, AtEH1/Pan1 and AtEH2/Pan1, although cytoplasmic proteins are not associated with the hexameric subcomplex in the cytoplasm. To investigate the dynamic assembly of the octameric TPC at the plasma membrane (PM), we performed state-of-the-art dual-color live cell imaging at physiological and lowered temperatures. Lowering the temperature slowed down endocytosis, thereby enhancing the temporal resolution of the differential recruitment of endocytic components. Under both normal and lowered temperature conditions, the core TPC subunit TPLATE and the AtEH/Pan1 proteins exhibited simultaneous recruitment at the PM. These results, together with co-localization analysis of different TPC subunits, allow us to conclude that TPC in plant cells is not recruited to the PM sequentially but as an octameric complex.
AU - Wang, J
AU - Mylle, E
AU - Johnson, Alexander J
AU - Besbrugge, N
AU - De Jaeger, G
AU - Friml, Jiří
AU - Pleskot, R
AU - van Damme, D
ID - 7695
IS - 3
JF - Plant Physiology
SN - 0032-0889
TI - High temporal resolution reveals simultaneous plasma membrane recruitment of TPLATE complex subunits
VL - 183
ER -
TY - JOUR
AB - * Morphogenesis and adaptive tropic growth in plants depend on gradients of the phytohormone auxin, mediated by the membrane‐based PIN‐FORMED (PIN) auxin transporters. PINs localize to a particular side of the plasma membrane (PM) or to the endoplasmic reticulum (ER) to directionally transport auxin and maintain intercellular and intracellular auxin homeostasis, respectively. However, the molecular cues that confer their diverse cellular localizations remain largely unknown.
* In this study, we systematically swapped the domains between ER‐ and PM‐localized PIN proteins, as well as between apical and basal PM‐localized PINs from Arabidopsis thaliana , to shed light on why PIN family members with similar topological structures reside at different membrane compartments within cells.
* Our results show that not only do the N‐ and C‐terminal transmembrane domains (TMDs) and central hydrophilic loop contribute to their differential subcellular localizations and cellular polarity, but that the pairwise‐matched N‐ and C‐terminal TMDs resulting from intramolecular domain–domain coevolution are also crucial for their divergent patterns of localization.
* These findings illustrate the complexity of the evolutionary path of PIN proteins in acquiring their plethora of developmental functions and adaptive growth in plants.
AU - Zhang, Yuzhou
AU - Hartinger, Corinna
AU - Wang, Xiaojuan
AU - Friml, Jiří
ID - 7697
IS - 5
JF - New Phytologist
SN - 0028-646X
TI - Directional auxin fluxes in plants by intramolecular domain‐domain co‐evolution of PIN auxin transporters
VL - 227
ER -
TY - JOUR
AB - Previously, we reported that the allelic de-etiolated by zinc (dez) and trichome birefringence (tbr) mutants exhibit photomorphogenic development in the dark, which is enhanced by high Zn. TRICHOME BIREFRINGENCE-LIKE proteins had been implicated in transferring acetyl groups to various hemicelluloses. Pectin O-acetylation levels were lower in dark-grown dez seedlings than in the wild type. We observed Zn-enhanced photomorphogenesis in the dark also in the reduced wall acetylation 2 (rwa2-3) mutant, which exhibits lowered O-acetylation levels of cell wall macromolecules including pectins and xyloglucans, supporting a role for cell wall macromolecule O-acetylation in the photomorphogenic phenotypes of rwa2-3 and dez. Application of very short oligogalacturonides (vsOGs) restored skotomorphogenesis in dark-grown dez and rwa2-3. Here we demonstrate that in dez, O-acetylation of non-pectin cell wall components, notably of xyloglucan, is enhanced. Our results highlight the complexity of cell wall homeostasis and indicate against an influence of xyloglucan O-acetylation on light-dependent seedling development.
AU - Sinclair, Scott A
AU - Gille, S.
AU - Pauly, M.
AU - Krämer, U.
ID - 7417
IS - 1
JF - Plant Signaling & Behavior
SN - 1559-2324
TI - Regulation of acetylation of plant cell wall components is complex and responds to external stimuli
VL - 15
ER -
TY - THES
AB - The plant hormone auxin plays indispensable roles in plant growth and development. An essential level of regulation in auxin action is the directional auxin transport within cells. The establishment of auxin gradient in plant tissue has been attributed to local auxin biosynthesis and directional intercellular auxin transport, which both are controlled by various environmental and developmental signals. It is well established that asymmetric auxin distribution in cells is achieved by polarly localized PIN-FORMED (PIN) auxin efflux transporters. Despite the initial insights into cellular mechanisms of PIN polarization obtained from the last decades, the molecular mechanism and specific regulators mediating PIN polarization remains elusive. In this thesis, we aim to find novel players in PIN subcellular polarity regulation during Arabidopsis development. We first characterize the physiological effect of piperonylic acid (PA) on Arabidopsis hypocotyl gravitropic bending and PIN polarization. Secondly, we reveal the importance of SCFTIR1/AFB auxin signaling pathway in shoot gravitropism bending termination. In addition, we also explore the role of myosin XI complex, and actin cytoskeleton in auxin feedback regulation on PIN polarity. In Chapter 1, we give an overview of the current knowledge about PIN-mediated auxin fluxes in various plant tropic responses. In Chapter 2, we study the physiological effect of PA on shoot gravitropic bending. Our results show that PA treatment inhibits auxin-mediated PIN3 repolarization by interfering with PINOID and PIN3 phosphorylation status, ultimately leading to hyperbending hypocotyls. In Chapter 3, we provide evidence to show that the SCFTIR1/AFB nuclear auxin signaling pathway is crucial and required for auxin-mediated PIN3 repolarization and shoot gravitropic bending termination. In Chapter 4, we perform a phosphoproteomics approach and identify the motor protein Myosin XI and its binding protein, the MadB2 family, as an essential regulator of PIN polarity for auxin-canalization related developmental processes. In Chapter 5, we demonstrate the vital role of actin cytoskeleton in auxin feedback on PIN polarity by regulating PIN subcellular trafficking. Overall, the data presented in this PhD thesis brings novel insights into the PIN polar localization regulation that resulted in the (re)establishment of the polar auxin flow and gradient in response to environmental stimuli during plant development.
AU - Han, Huibin
ID - 8589
SN - 2663-337X
TI - Novel insights into PIN polarity regulation during Arabidopsis development
ER -
TY - JOUR
AU - Han, Huibin
AU - Rakusova, Hana
AU - Verstraeten, Inge
AU - Zhang, Yuzhou
AU - Friml, Jiří
ID - 7643
IS - 5
JF - Plant Physiology
SN - 0032-0889
TI - SCF TIR1/AFB auxin signaling for bending termination during shoot gravitropism
VL - 183
ER -
TY - JOUR
AB - Earlier, we demonstrated that transcript levels of METAL TOLERANCE PROTEIN2 (MTP2) and of HEAVY METAL ATPase2 (HMA2) increase strongly in roots of Arabidopsis upon prolonged zinc (Zn) deficiency and respond to shoot physiological Zn status, and not to the local Zn status in roots. This provided evidence for shoot-to-root communication in the acclimation of plants to Zn deficiency. Zn-deficient soils limit both the yield and quality of agricultural crops and can result in clinically relevant nutritional Zn deficiency in human populations. Implementing Zn deficiency during cultivation of the model plant Arabidopsis thaliana on agar-solidified media is difficult because trace element contaminations are present in almost all commercially available agars. Here, we demonstrate root morphological acclimations to Zn deficiency on agar-solidified medium following the effective removal of contaminants. These advancements allow reproducible phenotyping toward understanding fundamental plant responses to deficiencies of Zn and other essential trace elements.
AU - Sinclair, Scott A
AU - Krämer, U.
ID - 7416
IS - 1
JF - Plant Signaling & Behavior
SN - 1559-2324
TI - Generation of effective zinc-deficient agar-solidified media allows identification of root morphology changes in response to zinc limitation
VL - 15
ER -
TY - JOUR
AB - The widely used non-steroidal anti-inflammatory drugs (NSAIDs) are derivatives of the phytohormone salicylic acid (SA). SA is well known to regulate plant immunity and development, whereas there have been few reports focusing on the effects of NSAIDs in plants. Our studies here reveal that NSAIDs exhibit largely overlapping physiological activities to SA in the model plant Arabidopsis. NSAID treatments lead to shorter and agravitropic primary roots and inhibited lateral root organogenesis. Notably, in addition to the SA-like action, which in roots involves binding to the protein phosphatase 2A (PP2A), NSAIDs also exhibit PP2A-independent effects. Cell biological and biochemical analyses reveal that many NSAIDs bind directly to and inhibit the chaperone activity of TWISTED DWARF1, thereby regulating actin cytoskeleton dynamics and subsequent endosomal trafficking. Our findings uncover an unexpected bioactivity of human pharmaceuticals in plants and provide insights into the molecular mechanism underlying the cellular action of this class of anti-inflammatory compounds.
AU - Tan, Shutang
AU - Di Donato, Martin
AU - Glanc, Matous
AU - Zhang, Xixi
AU - Klíma, Petr
AU - Liu, Jie
AU - Bailly, Aurélien
AU - Ferro, Noel
AU - Petrášek, Jan
AU - Geisler, Markus
AU - Friml, Jiří
ID - 8943
IS - 9
JF - Cell Reports
TI - Non-steroidal anti-inflammatory drugs target TWISTED DWARF1-regulated actin dynamics and auxin transport-mediated plant development
VL - 33
ER -
TY - JOUR
AB - Wound healing in plant tissues, consisting of rigid cell wall-encapsulated cells, represents a considerable challenge and occurs through largely unknown mechanisms distinct from those in animals. Owing to their inability to migrate, plant cells rely on targeted cell division and expansion to regenerate wounds. Strict coordination of these wound-induced responses is essential to ensure efficient, spatially restricted wound healing. Single-cell tracking by live imaging allowed us to gain mechanistic insight into the wound perception and coordination of wound responses after laser-based wounding in Arabidopsis root. We revealed a crucial contribution of the collapse of damaged cells in wound perception and detected an auxin increase specific to cells immediately adjacent to the wound. This localized auxin increase balances wound-induced cell expansion and restorative division rates in a dose-dependent manner, leading to tumorous overproliferation when the canonical TIR1 auxin signaling is disrupted. Auxin and wound-induced turgor pressure changes together also spatially define the activation of key components of regeneration, such as the transcription regulator ERF115. Our observations suggest that the wound signaling involves the sensing of collapse of damaged cells and a local auxin signaling activation to coordinate the downstream transcriptional responses in the immediate wound vicinity.
AU - Hörmayer, Lukas
AU - Montesinos López, Juan C
AU - Marhavá, Petra
AU - Benková, Eva
AU - Yoshida, Saiko
AU - Friml, Jiří
ID - 8002
IS - 26
JF - Proceedings of the National Academy of Sciences
SN - 0027-8424
TI - Wounding-induced changes in cellular pressure and localized auxin signalling spatially coordinate restorative divisions in roots
VL - 117
ER -
TY - JOUR
AB - Plants, like other multicellular organisms, survive through a delicate balance between growth and defense against pathogens. Salicylic acid (SA) is a major defense signal in plants, and the perception mechanism as well as downstream signaling activating the immune response are known. Here, we identify a parallel SA signaling that mediates growth attenuation. SA directly binds to A subunits of protein phosphatase 2A (PP2A), inhibiting activity of this complex. Among PP2A targets, the PIN2 auxin transporter is hyperphosphorylated in response to SA, leading to changed activity of this important growth regulator. Accordingly, auxin transport and auxin-mediated root development, including growth, gravitropic response, and lateral root organogenesis, are inhibited. This study reveals how SA, besides activating immunity, concomitantly attenuates growth through crosstalk with the auxin distribution network. Further analysis of this dual role of SA and characterization of additional SA-regulated PP2A targets will provide further insights into mechanisms maintaining a balance between growth and defense.
AU - Tan, Shutang
AU - Abas, Melinda F
AU - Verstraeten, Inge
AU - Glanc, Matous
AU - Molnar, Gergely
AU - Hajny, Jakub
AU - Lasák, Pavel
AU - Petřík, Ivan
AU - Russinova, Eugenia
AU - Petrášek, Jan
AU - Novák, Ondřej
AU - Pospíšil, Jiří
AU - Friml, Jiří
ID - 7427
IS - 3
JF - Current Biology
SN - 09609822
TI - Salicylic acid targets protein phosphatase 2A to attenuate growth in plants
VL - 30
ER -
TY - JOUR
AB - Plant survival depends on vascular tissues, which originate in a self‐organizing manner as strands of cells co‐directionally transporting the plant hormone auxin. The latter phenomenon (also known as auxin canalization) is classically hypothesized to be regulated by auxin itself via the effect of this hormone on the polarity of its own intercellular transport. Correlative observations supported this concept, but molecular insights remain limited.
In the current study, we established an experimental system based on the model Arabidopsis thaliana, which exhibits auxin transport channels and formation of vasculature strands in response to local auxin application.
Our methodology permits the genetic analysis of auxin canalization under controllable experimental conditions. By utilizing this opportunity, we confirmed the dependence of auxin canalization on a PIN‐dependent auxin transport and nuclear, TIR1/AFB‐mediated auxin signaling. We also show that leaf venation and auxin‐mediated PIN repolarization in the root require TIR1/AFB signaling.
Further studies based on this experimental system are likely to yield better understanding of the mechanisms underlying auxin transport polarization in other developmental contexts.
AU - Mazur, E
AU - Kulik, Ivan
AU - Hajny, Jakub
AU - Friml, Jiří
ID - 7500
IS - 5
JF - New Phytologist
SN - 0028-646x
TI - Auxin canalization and vascular tissue formation by TIR1/AFB-mediated auxin signaling in arabidopsis
VL - 226
ER -