title: Non-centrosomal nucleation mediated by augmin organizes microtubules in post-mitotic neurons and controls axonal microtubule polarity.
abstract: Neurons display a highly polarized microtubule network that mediates trafficking throughout the extensive cytoplasm and is crucial for neuronal differentiation and function. In newborn migrating neurons, the microtubule network is organized by the centrosome. During neuron maturation, however, the centrosome gradually loses this activity, and how microtubules are organized in more mature neurons remains poorly understood. Here, we demonstrate that microtubule organization in post-mitotic neurons strongly depends on non-centrosomal nucleation mediated by augmin and by the nucleator γTuRC. Disruption of either complex not only reduces microtubule density but also microtubule bundling. These microtubule defects impair neurite formation, interfere with axon specification and growth, and disrupt axonal trafficking. In axons augmin does not merely mediate nucleation of microtubules but ensures their uniform plus end-out orientation. Thus, the augmin-γTuRC module, initially identified in mitotic cells, may be commonly used to generate and maintain microtubule configurations with specific polarity.
authors.affiliation: Institute for Research in Biomedicine (IRB Barcelona), The Barcelona Institute of Science and Technology, Baldiri Reixac 10, 08028 Barcelona, Spain.
authors.forename: Carlos
authors.initials: C
authors.lastname: Sánchez-Huertas
authors.affiliation: Institute for Research in Biomedicine (IRB Barcelona), The Barcelona Institute of Science and Technology, Baldiri Reixac 10, 08028 Barcelona, Spain.
authors.forename: Francisco
authors.initials: F
authors.lastname: Freixo
authors.affiliation: Institute for Research in Biomedicine (IRB Barcelona), The Barcelona Institute of Science and Technology, Baldiri Reixac 10, 08028 Barcelona, Spain.
authors.forename: Ricardo
authors.identifier: 0000-0002-8146-3693
authors.initials: R
authors.lastname: Viais
authors.affiliation: Institute for Research in Biomedicine (IRB Barcelona), The Barcelona Institute of Science and Technology, Baldiri Reixac 10, 08028 Barcelona, Spain.
authors.forename: Cristina
authors.initials: C
authors.lastname: Lacasa
authors.affiliation: Department of Cell Biology, Physiology and Immunology, Faculty of Biology and INUB, University of Barcelona, Barcelona 08028, Spain.|Centro de Investigación Biomédica en Red sobre Enfermedades Neurodegenerativas (CIBERNED), ISCIII, Madrid 28031, Spain.|Vall d'Hebron Institute of Research, Barcelona 08035, Spain.|Institució Catalana de Recerca i Estudis Avançats (ICREA), Barcelona 08010, Spain.
authors.forename: Eduardo
authors.initials: E
authors.lastname: Soriano
authors.affiliation: Institute for Research in Biomedicine (IRB Barcelona), The Barcelona Institute of Science and Technology, Baldiri Reixac 10, 08028 Barcelona, Spain.
authors.forename: Jens
authors.initials: J
authors.lastname: Lüders
mesh_terms: D000818:Animals; D001370:Axonal Transport; D001369:Axons / Q000378:metabolism; D016764:Cell Polarity; D018385:Centrosome; D051379:Mice; D008869:Microtubule-Associated Proteins / Q000378:metabolism*; D022101:Microtubule-Organizing Center; D008870:Microtubules / Q000378:metabolism*; D046912:Multiprotein Complexes / Q000378:metabolism; D016501:Neurites / Q000378:metabolism; D055495:Neurogenesis; D009474:Neurons / Q000166:cytology / Q000378:metabolism*; D064047:Spindle Poles / Q000378:metabolism; D014404:Tubulin / Q000378:metabolism*
chemical_list: D008869:Microtubule-Associated Proteins; D046912:Multiprotein Complexes; C583407:TUBG1 protein, mouse; D014404:Tubulin