TY - JOUR AB - The phytohormone auxin is vital to plant growth and development. A unique property of auxin among all other plant hormones is its cell-to-cell polar transport that requires activity of polarly localized PIN-FORMED (PIN) auxin efflux transporters. Despite the substantial molecular insight into the cellular PIN polarization, the mechanistic understanding for developmentally and environmentally regulated PIN polarization is scarce. The long-standing belief that auxin modulates its own transport by means of a positive feedback mechanism has inspired both experimentalists and theoreticians for more than two decades. Recently, theoretical models for auxin-dependent patterning in plants include the feedback between auxin transport and the PIN protein localization. These computer models aid to assess the complexity of plant development by testing and predicting plausible scenarios for various developmental processes that occur in planta. Although the majority of these models rely on purely heuristic principles, the most recent mechanistic models tentatively integrate biologically testable components into known cellular processes that underlie the PIN polarity regulation. The existing and emerging computational approaches to describe PIN polarization are presented and discussed in the light of recent experimental data on the PIN polar targeting. AU - Wabnik, Krzysztof T AU - Govaerts, Willy AU - Friml, Jirí AU - Kleine Vehn, Jürgen ID - 3092 IS - 8 JF - Molecular BioSystems TI - Feedback models for polarized auxin transport: An emerging trend VL - 7 ER - TY - JOUR AB - The phytohormone auxin is an important determinant of plant development. Directional auxin flow within tissues depends on polar localization of PIN auxin transporters. To explore regulation of PIN-mediated auxin transport, we screened for suppressors of PIN1 overexpression (supo) and identified an inositol polyphosphate 1-phosphatase mutant (supo1), with elevated inositol trisphosphate (InsP 3) and cytosolic Ca 2+ levels. Pharmacological and genetic increases in InsP 3 or Ca 2+ levels also suppressed the PIN1 gain-of-function phenotypes and caused defects in basal PIN localization, auxin transport and auxin-mediated development. In contrast, the reductions in InsP 3 levels and Ca 2+ signaling antagonized the effects of the supo1 mutation and disrupted preferentially apical PIN localization. InsP 3 and Ca 2+ are evolutionarily conserved second messengers involved in various cellular functions, particularly stress responses. Our findings implicate them as modifiers of cell polarity and polar auxin transport, and highlight a potential integration point through which Ca 2+ signaling-related stimuli could influence auxin-mediated development. AU - Zhang, Jing AU - Vanneste, Steffen AU - Brewer, Philip B AU - Michniewicz, Marta AU - Peter Grones AU - Kleine-Vehn, Jürgen AU - Löfke, Christian AU - Teichmann, Thomas AU - Bielach, Agnieszka AU - Cannoot, Bernard AU - Hoyerová, Klára AU - Xu Chen AU - Xue, Hong-Wei AU - Eva Benková AU - Zažímalová, Eva AU - Jirí Friml ID - 3089 IS - 6 JF - Developmental Cell TI - Inositol trisphosphate-induced ca^2+ signaling modulates auxin transport and pin polarity VL - 20 ER - TY - JOUR AB - The polarized transport of the phytohormone auxin [1], which is crucial for the regulation of different stages of plant development [2, 3], depends on the asymmetric plasma membrane distribution of the PIN-FORMED (PIN) auxin efflux carriers [4, 5]. The PIN polar localization results from clathrin-mediated endocytosis (CME) from the plasma membrane and subsequent polar recycling [6]. The Arabidopsis genome encodes two groups of dynamin-related proteins (DRPs) that show homology to mammalian dynamin - a protein required for fission of endocytic vesicles during CME [7, 8]. Here we show by coimmunoprecipitation (coIP), bimolecular fluorescence complementation (BiFC), and Förster resonance energy transfer (FRET) that members of the DRP1 group closely associate with PIN proteins at the cell plate. Localization and phenotypic analysis of novel drp1 mutants revealed a requirement for DRP1 function in correct PIN distribution and in auxin-mediated development. We propose that rapid and specific internalization of PIN proteins mediated by the DRP1 proteins and the associated CME machinery from the cell plate membranes during cytokinesis is an important mechanism for proper polar PIN positioning in interphase cells. AU - Mravec, Jozef AU - Petrášek, Jan AU - Li, Na AU - Boeren, Sjef AU - Karlova, Rumyana AU - Kitakura, Saeko AU - Pařezová, Markéta AU - Naramoto, Satoshi AU - Nodzyński, Thomasz AU - Dhonukshe, Pankaj AU - Bednarek, Sebastian Y AU - Zažímalová, Eva AU - De Vries, Sacco AU - Jirí Friml ID - 3090 IS - 12 JF - Current Biology TI - Cell plate restricted association of DRP1A and PIN proteins is required for cell polarity establishment in arabidopsis VL - 21 ER - TY - JOUR AB - Background: Whereas the majority of animals develop toward a predetermined body plan, plants show iterative growth and continually produce new organs and structures from actively dividing meristems. This raises an intriguing question: How are these newly developed organs patterned? In Arabidopsis embryos, radial symmetry is broken by the bisymmetric specification of the cotyledons in the apical domain. Subsequently, this bisymmetry is propagated to the root promeristem. Results: Here we present a mutually inhibitory feedback loop between auxin and cytokinin that sets distinct boundaries of hormonal output. Cytokinins promote the bisymmetric distribution of the PIN-FORMED (PIN) auxin efflux proteins, which channel auxin toward a central domain. High auxin promotes transcription of the cytokinin signaling inhibitor AHP6, which closes the interaction loop. This bisymmetric auxin response domain specifies the differentiation of protoxylem in a bisymmetric pattern. In embryonic roots, cytokinin is required to translate a bisymmetric auxin response in the cotyledons to a bisymmetric vascular pattern in the root promeristem. Conclusions: Our results present an interactive feedback loop between hormonal signaling and transport by which small biases in hormonal input are propagated into distinct signaling domains to specify the vascular pattern in the root meristem. It is an intriguing possibility that such a mechanism could transform radial patterns and allow continuous vascular connections between other newly emerging organs. AU - Bishopp, Anthony AU - Help, Hanna AU - El-Showk, Sedeer AU - Weijers, Dolf AU - Scheres, Ben AU - Jirí Friml AU - Eva Benková AU - Mähönen, Ari Pekka AU - Helariutta, Ykä ID - 3088 IS - 11 JF - Current Biology TI - A mutually inhibitory interaction between auxin and cytokinin specifies vascular pattern in roots VL - 21 ER - TY - JOUR AB - Plants take up iron from the soil using the IRON-REGULATED TRANSPORTER 1 (IRT1) high-affinity iron transporter at the root surface. Sophisticated regulatory mechanisms allow plants to tightly control the levels of IRT1, ensuring optimal absorption of essential but toxic iron. Here, we demonstrate that overexpression of Arabidopsis thaliana IRT1 leads to constitutive IRT1 protein accumulation, metal overload, and oxidative stress. IRT1 is unexpectedly found in trans-Golgi network/early endosomes of root hair cells, and its levels and localization are unaffected by iron nutrition. Using pharmacological approaches, we show that IRT1 cycles to the plasma membrane to perform iron and metal uptake at the cell surface and is sent to the vacuole for proper turnover. We also prove that IRT1 is monoubiquitinated on several cytosol-exposed residues in vivo and that mutation of two putative monoubiquitination target residues in IRT1 triggers stabilization at the plasma membrane and leads to extreme lethality. Together, these data suggest a model in which monoubiquitin-dependent internalization/sorting and turnover keep the plasma membrane pool of IRT1 low to ensure proper iron uptake and to prevent metal toxicity. More generally, our work demonstrates the existence of monoubiquitin-dependent trafficking to lytic vacuoles in plants and points to proteasome-independent turnover of plasma membrane proteins. AU - Barberon, Marie AU - Zelazny, Enric AU - Robert, Stéphanie AU - Conéjéro, Geneviève AU - Curie, Cathy AU - Jirí Friml AU - Vert, Grégory ID - 3093 IS - 32 JF - PNAS TI - Monoubiquitin dependent endocytosis of the Iron Regulated Transporter 1 IRT1 transporter controls iron uptake in plants VL - 108 ER - TY - JOUR AB - Summary Gravitropism aligns plant growth with gravity. It involves gravity perception and the asymmetric distribution of the phytohormone auxin. Here we provide insights into the mechanism for hypocotyl gravitropic growth. We show that the Arabidopsis thaliana PIN3 auxin transporter is required for the asymmetric auxin distribution for the gravitropic response. Gravistimulation polarizes PIN3 to the bottom side of hypocotyl endodermal cells, which correlates with an increased auxin response at the lower hypocotyl side. Both PIN3 polarization and hypocotyl bending require the activity of the trafficking regulator GNOM and the protein kinase PINOID. Our data suggest that gravity-induced PIN3 polarization diverts the auxin flow to mediate the asymmetric distribution of auxin for gravitropic shoot bending. AU - Rakusová, Hana AU - Gallego-Bartolomé, Javier AU - Vanstraelen, Marleen AU - Robert, Hélène S AU - Alabadí, David AU - Blázquez, Miguel A AU - Eva Benková AU - Jirí Friml ID - 3094 IS - 5 JF - Plant Journal TI - Polarization of PIN3 dependent auxin transport for hypocotyl gravitropic response in Arabidopsis thaliana VL - 67 ER - TY - JOUR AU - Sauer, Michael AU - Friml, Jirí ID - 3091 JF - Molecular Systems Biology TI - Fleeting hormone cues get stabilized for plant organogenesis VL - 7 ER - TY - JOUR AB - Multicellular organisms depend on cell production, cell fate specification, and correct patterning to shape their adult body. In plants, auxin plays a prominent role in the timely coordination of these different cellular processes. A well-studied example is lateral root initiation, in which auxin triggers founder cell specification and cell cycle activation of xylem pole–positioned pericycle cells. Here, we report that the E2Fa transcription factor of Arabidopsis thaliana is an essential component that regulates the asymmetric cell division marking lateral root initiation. Moreover, we demonstrate that E2Fa expression is regulated by the LATERAL ORGAN BOUNDARY DOMAIN18/LATERAL ORGAN BOUNDARY DOMAIN33 (LBD18/LBD33) dimer that is, in turn, regulated by the auxin signaling pathway. LBD18/LBD33 mediates lateral root organogenesis through E2Fa transcriptional activation, whereas E2Fa expression under control of the LBD18 promoter eliminates the need for LBD18. Besides lateral root initiation, vascular patterning is disrupted in E2Fa knockout plants, similarly as it is affected in auxin signaling and lbd mutants, indicating that the transcriptional induction of E2Fa through LBDs represents a general mechanism for auxin-dependent cell cycle activation. Our data illustrate how a conserved mechanism driving cell cycle entry has been adapted evolutionarily to connect auxin signaling with control of processes determining plant architecture. AU - Berckmans, Barbara AU - Vassileva, Valya AU - Schmid, Stephan P AU - Maes, Sara AU - Parizot, Boris AU - Naramoto, Satoshi AU - Magyar, Zoltan AU - Lessa Alvim Kamei, Claire AU - Koncz, Csaba AU - Bögre, Laszlo AU - Persiau, Geert AU - De Jaeger, Geert AU - Jirí Friml AU - Simon, Rüdiger AU - Beeckman, Tom AU - de Veyldera, Lieven ID - 3102 IS - 10 JF - Plant Cell TI - Auxin Dependent cell cycle reactivation through transcriptional regulation of arabidopsis E2Fa by lateral organ boundary proteins VL - 23 ER - TY - JOUR AB - Endocytosis in plants has an essential role not only for basic cellular functions but also for growth and development, hormonal signaling and communication with the environment including nutrient delivery, toxin avoidance, and pathogen defense. The major endocytic mechanism in plants depends on the coat protein clathrin. It starts by clathrin-coated vesicle formation at the plasma membrane, where specific cargoes are recognized and packaged for internalization. Recently, genetic, biochemical and advanced microscopy studies provided initial insights into mechanisms and roles of clathrin-mediated endocytosis in plants. Here we summarize the present state of knowledge and compare mechanisms of clathrin-mediated endocytosis in plants with animal and yeast paradigms as well as review plant-specific regulations and roles of this process. AU - Chen, Xu AU - Irani, Niloufer AU - Friml, Jirí ID - 3103 IS - 6 JF - Current Opinion in Plant Biology TI - Clathrin-mediated endocytosis: The gateway into plant cells VL - 14 ER - TY - JOUR AB - Cancer cell of origin is difficult to identify by analyzing cells within terminal stage tumors, whose identity could be concealed by the acquired plasticity. Thus, an ideal approach to identify the cell of origin is to analyze proliferative abnormalities in distinct lineages prior to malignancy. Here, we use mosaic analysis with double markers (MADM) in mice to model gliomagenesis by initiating concurrent p53/Nf1 mutations sporadically in neural stem cells (NSCs). Surprisingly, MADM-based lineage tracing revealed significant aberrant growth prior to malignancy only in oligodendrocyte precursor cells (OPCs), but not in any other NSC-derived lineages or NSCs themselves. Upon tumor formation, phenotypic and transcriptome analyses of tumor cells revealed salient OPC features. Finally, introducing the same p53/Nf1 mutations directly into OPCs consistently led to gliomagenesis. Our findings suggest OPCs as the cell of origin in this model, even when initial mutations occur in NSCs, and highlight the importance of analyzing premalignant stages to identify the cancer cell of origin. AU - Liu, Chong AU - Sage, Jonathan C AU - Miller, Michael R AU - Verhaak, Roel G AU - Simon Hippenmeyer AU - Vogel, Hannes AU - Foreman, Oded AU - Bronson, Roderick T AU - Nishiyama, Akiko AU - Luo, Liqun AU - Zong, Hui ID - 3147 IS - 2 JF - Cell TI - Mosaic analysis with double markers reveals tumor cell of origin in glioma VL - 146 ER -