TY - JOUR AB - Centrosomes play a crucial role during immune cell interactions and initiation of the immune response. In proliferating cells, centrosome numbers are tightly controlled and generally limited to one in G1 and two prior to mitosis. Defects in regulating centrosome numbers have been associated with cell transformation and tumorigenesis. Here, we report the emergence of extra centrosomes in leukocytes during immune activation. Upon antigen encounter, dendritic cells pass through incomplete mitosis and arrest in the subsequent G1 phase leading to tetraploid cells with accumulated centrosomes. In addition, cell stimulation increases expression of polo-like kinase 2, resulting in diploid cells with two centrosomes in G1-arrested cells. During cell migration, centrosomes tightly cluster and act as functional microtubule-organizing centers allowing for increased persistent locomotion along gradients of chemotactic cues. Moreover, dendritic cells with extra centrosomes display enhanced secretion of inflammatory cytokines and optimized T cell responses. Together, these results demonstrate a previously unappreciated role of extra centrosomes for regular cell and tissue homeostasis. AU - Weier, Ann-Kathrin AU - Homrich, Mirka AU - Ebbinghaus, Stephanie AU - Juda, Pavel AU - Miková, Eliška AU - Hauschild, Robert AU - Zhang, Lili AU - Quast, Thomas AU - Mass, Elvira AU - Schlitzer, Andreas AU - Kolanus, Waldemar AU - Burgdorf, Sven AU - Gruß, Oliver J. AU - Hons, Miroslav AU - Wieser, Stefan AU - Kiermaier, Eva ID - 12122 IS - 12 JF - Journal of Cell Biology KW - Cell Biology SN - 0021-9525 TI - Multiple centrosomes enhance migration and immune cell effector functions of mature dendritic cells VL - 221 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 - JOUR AB - The mammalian neocortex is composed of diverse neuronal and glial cell classes that broadly arrange in six distinct laminae. Cortical layers emerge during development and defects in the developmental programs that orchestrate cortical lamination are associated with neurodevelopmental diseases. The developmental principle of cortical layer formation depends on concerted radial projection neuron migration, from their birthplace to their final target position. Radial migration occurs in defined sequential steps, regulated by a large array of signaling pathways. However, based on genetic loss-of-function experiments, most studies have thus far focused on the role of cell-autonomous gene function. Yet, cortical neuron migration in situ is a complex process and migrating neurons traverse along diverse cellular compartments and environments. The role of tissue-wide properties and genetic state in radial neuron migration is however not clear. Here we utilized mosaic analysis with double markers (MADM) technology to either sparsely or globally delete gene function, followed by quantitative single-cell phenotyping. The MADM-based gene ablation paradigms in combination with computational modeling demonstrated that global tissue-wide effects predominate cell-autonomous gene function albeit in a gene-specific manner. Our results thus suggest that the genetic landscape in a tissue critically affects the overall migration phenotype of individual cortical projection neurons. In a broader context, our findings imply that global tissue-wide effects represent an essential component of the underlying etiology associated with focal malformations of cortical development in particular, and neurological diseases in general. AU - Hansen, Andi H AU - Pauler, Florian AU - Riedl, Michael AU - Streicher, Carmen AU - Heger, Anna-Magdalena AU - Laukoter, Susanne AU - Sommer, Christoph M AU - Nicolas, Armel AU - Hof, Björn AU - Tsai, Li Huei AU - Rülicke, Thomas AU - Hippenmeyer, Simon ID - 10791 IS - 1 JF - Oxford Open Neuroscience TI - Tissue-wide effects override cell-intrinsic gene function in radial neuron migration VL - 1 ER - TY - JOUR AB - When crawling through the body, leukocytes often traverse tissues that are densely packed with extracellular matrix and other cells, and this raises the question: How do leukocytes overcome compressive mechanical loads? Here, we show that the actin cortex of leukocytes is mechanoresponsive and that this responsiveness requires neither force sensing via the nucleus nor adhesive interactions with a substrate. Upon global compression of the cell body as well as local indentation of the plasma membrane, Wiskott-Aldrich syndrome protein (WASp) assembles into dot-like structures, providing activation platforms for Arp2/3 nucleated actin patches. These patches locally push against the external load, which can be obstructing collagen fibers or other cells, and thereby create space to facilitate forward locomotion. We show in vitro and in vivo that this WASp function is rate limiting for ameboid leukocyte migration in dense but not in loose environments and is required for trafficking through diverse tissues such as skin and lymph nodes. AU - Gaertner, Florian AU - Reis-Rodrigues, Patricia AU - De Vries, Ingrid AU - Hons, Miroslav AU - Aguilera, Juan AU - Riedl, Michael AU - Leithner, Alexander F AU - Tasciyan, Saren AU - Kopf, Aglaja AU - Merrin, Jack AU - Zheden, Vanessa AU - Kaufmann, Walter AU - Hauschild, Robert AU - Sixt, Michael K ID - 10703 IS - 1 JF - Developmental Cell SN - 1534-5807 TI - WASp triggers mechanosensitive actin patches to facilitate immune cell migration in dense tissues VL - 57 ER - TY - GEN AU - Schlögl, Alois AU - Elefante, Stefano AU - Hornoiu, Andrei AU - Stadlbauer, Stephan ID - 12909 SN - 978-961-6980-77-7 T2 - ASHPC21 – Austrian-Slovenian HPC Meeting 2021 TI - Managing software on a heterogenous HPC cluster ER -