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Non-centrosomal nucleation mediated by augmin organizes microtubules in post-mitotic neurons and controls axonal microtubule polarity

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 c...

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Autores principales: Sánchez-Huertas, Carlos, Freixo, Francisco, Viais, Ricardo, Lacasa, Cristina, Soriano, Eduardo, Lüders, Jens
Formato: Online Artículo Texto
Lenguaje:English
Publicado: Nature Publishing Group 2016
Materias:
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC4947180/
https://www.ncbi.nlm.nih.gov/pubmed/27405868
http://dx.doi.org/10.1038/ncomms12187
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author Sánchez-Huertas, Carlos
Freixo, Francisco
Viais, Ricardo
Lacasa, Cristina
Soriano, Eduardo
Lüders, Jens
author_facet Sánchez-Huertas, Carlos
Freixo, Francisco
Viais, Ricardo
Lacasa, Cristina
Soriano, Eduardo
Lüders, Jens
author_sort Sánchez-Huertas, Carlos
collection PubMed
description 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.
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spelling pubmed-49471802016-07-27 Non-centrosomal nucleation mediated by augmin organizes microtubules in post-mitotic neurons and controls axonal microtubule polarity Sánchez-Huertas, Carlos Freixo, Francisco Viais, Ricardo Lacasa, Cristina Soriano, Eduardo Lüders, Jens Nat Commun Article 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. Nature Publishing Group 2016-07-13 /pmc/articles/PMC4947180/ /pubmed/27405868 http://dx.doi.org/10.1038/ncomms12187 Text en Copyright © 2016, Nature Publishing Group, a division of Macmillan Publishers Limited. All Rights Reserved. http://creativecommons.org/licenses/by/4.0/ This work is licensed under a Creative Commons Attribution 4.0 International License. The images or other third party material in this article are included in the article's Creative Commons license, unless indicated otherwise in the credit line; if the material is not included under the Creative Commons license, users will need to obtain permission from the license holder to reproduce the material. To view a copy of this license, visit http://creativecommons.org/licenses/by/4.0/
spellingShingle Article
Sánchez-Huertas, Carlos
Freixo, Francisco
Viais, Ricardo
Lacasa, Cristina
Soriano, Eduardo
Lüders, Jens
Non-centrosomal nucleation mediated by augmin organizes microtubules in post-mitotic neurons and controls axonal microtubule polarity
title Non-centrosomal nucleation mediated by augmin organizes microtubules in post-mitotic neurons and controls axonal microtubule polarity
title_full Non-centrosomal nucleation mediated by augmin organizes microtubules in post-mitotic neurons and controls axonal microtubule polarity
title_fullStr Non-centrosomal nucleation mediated by augmin organizes microtubules in post-mitotic neurons and controls axonal microtubule polarity
title_full_unstemmed Non-centrosomal nucleation mediated by augmin organizes microtubules in post-mitotic neurons and controls axonal microtubule polarity
title_short Non-centrosomal nucleation mediated by augmin organizes microtubules in post-mitotic neurons and controls axonal microtubule polarity
title_sort non-centrosomal nucleation mediated by augmin organizes microtubules in post-mitotic neurons and controls axonal microtubule polarity
topic Article
url https://www.ncbi.nlm.nih.gov/pmc/articles/PMC4947180/
https://www.ncbi.nlm.nih.gov/pubmed/27405868
http://dx.doi.org/10.1038/ncomms12187
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