Microtubule stabilization drives 3D centrosome migration to initiate primary ciliogenesis

Abstract

The classical view of centrosome decentering and migration to the cell periphery during ciliogenesis is that it is pulled toward its final destination. Here, Pitaval et al. argue that microtubule stabilization in the early stages of ciliogenesis generates pushing forces that propel the centrosome toward the apical pole.

Abstract

Primary cilia are sensory organelles located at the cell surface. Their assembly is primed by centrosome migration to the apical surface, yet surprisingly little is known about this initiating step. To gain insight into the mechanisms driving centrosome migration, we exploited the reproducibility of cell architecture on adhesive micropatterns to investigate the cytoskeletal remodeling supporting it. Microtubule network densification and bundling, with the transient formation of an array of cold-stable microtubules, and actin cytoskeleton asymmetrical contraction participate in concert to drive apical centrosome migration. The distal appendage protein Cep164 appears to be a key actor involved in the cytoskeleton remodeling and centrosome migration, whereas intraflagellar transport 88’s role seems to be restricted to axoneme elongation. Together, our data elucidate the hitherto unexplored mechanism of centrosome migration and show that it is driven by the increase and clustering of mechanical forces to push the centrosome toward the cell apical pole.

Journal

Journal ID (nlm-ta): J Cell Biol

Journal ID (iso-abbrev): J. Cell Biol

Journal ID (publisher-id): jcb

Journal ID (hwp): jcb

Title: The Journal of Cell Biology

Publisher: The Rockefeller University Press

ISSN (Print): 0021-9525

ISSN (Electronic): 1540-8140

Publication date (Print): 06 November 2017

Volume: 216

Issue: 11

Pages: 3713-3728

Affiliations

[1 ]UMR_S 1038, Biomics Lab, University Grenoble-Alpes, Commissariat à l'Énergie Atomique et aux Énergies Alternatives, Institut National de la Santé et de la Recherche, Institut de Biosciences et Biotechnologies de Grenoble, Grenoble, France

[2 ]UMR 5168, CytoMorpho Lab, University Grenoble-Alpes, Commissariat à l'Énergie Atomique et aux Énergies Alternatives, Institut National de la Recherche Agronomique, Centre National de la Recherche Scientifique, Institut de Biosciences et Biotechnologies de Grenoble, Grenoble, France

[3 ]UMR_S 1036, Biologie du Cancer et de l'Infection, University Grenoble-Alpes, Commissariat à l'Énergie Atomique et aux Énergies Alternatives, Institut National de la Santé et de la Recherche, Institut de Biosciences et Biotechnologies de Grenoble, Grenoble, France

[4 ]UMRS 1160, CytoMorpho Lab, University Paris Diderot, Institut National de la Santé et de la Recherche, Hôpital Saint Louis, Institut Universitaire d’Hematologie, Paris, France

Author notes

Correspondence to Manuel Théry: manuel.thery@ 123456cea.fr ;

James Sillibourne: sillibou@ 123456gmail.com

J. Sillibourne’s present address is Autolus Limited, London, England, UK.

Article

Publisher ID: 201610039

DOI: 10.1083/jcb.201610039

PMC ID: 5674878

PubMed ID: 28993469

Copyright statement: © 2017 Pitaval et al.

License:

This article is distributed under the terms of an Attribution–Noncommercial–Share Alike–No Mirror Sites license for the first six months after the publication date (see http://www.rupress.org/terms/). After six months it is available under a Creative Commons License (Attribution–Noncommercial–Share Alike 4.0 International license, as described at https://creativecommons.org/licenses/by-nc-sa/4.0/).

Product

Funding

Funded by: European Research Council, DOI http://dx.doi.org/10.13039/100010663;

Award ID: SpiCy 310472

Categories

Subject: Research Articles

Subject: Article

Subject: 25

Subject: 10