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      Microtubule stabilization drives 3D centrosome migration to initiate primary ciliogenesis

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          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.

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          Most cited references55

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          Centrioles, centrosomes, and cilia in health and disease.

          Centrioles are barrel-shaped structures that are essential for the formation of centrosomes, cilia, and flagella. Here we review recent advances in our understanding of the function and biogenesis of these organelles, and we emphasize their connection to human disease. Deregulation of centrosome numbers has long been proposed to contribute to genome instability and tumor formation, whereas mutations in centrosomal proteins have recently been genetically linked to microcephaly and dwarfism. Finally, structural or functional centriole aberrations contribute to ciliopathies, a variety of complex diseases that stem from the absence or dysfunction of cilia.
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            Cep164, a novel centriole appendage protein required for primary cilium formation

            Primary cilia (PC) function as microtubule-based sensory antennae projecting from the surface of many eukaryotic cells. They play important roles in mechano- and chemosensory perception and their dysfunction is implicated in developmental disorders and severe diseases. The basal body that functions in PC assembly is derived from the mature centriole, a component of the centrosome. Through a small interfering RNA screen we found several centrosomal proteins (Ceps) to be involved in PC formation. One newly identified protein, Cep164, was indispensable for PC formation and hence characterized in detail. By immunogold electron microscopy, Cep164 could be localized to the distal appendages of mature centrioles. In contrast to ninein and Cep170, two components of subdistal appendages, Cep164 persisted at centrioles throughout mitosis. Moreover, the localizations of Cep164 and ninein/Cep170 were mutually independent during interphase. These data implicate distal appendages in PC formation and identify Cep164 as an excellent marker for these structures.
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              The centrosome in cells and organisms.

              The centrosome acts as the main microtubule-nucleating organelle in animal cells and plays a critical role in mitotic spindle orientation and in genome stability. Yet, despite its central role in cell biology, the centrosome is not present in all multicellular organisms or in all cells of a given organism. The main outcome of centrosome reproduction is the transmission of polarity to daughter cells and, in most animal species, the sperm-donated centrosome defines embryo polarity. Here I will discuss the role of the centrosome in cell polarity, resulting from its ability to position the nucleus at the cell center, and discuss how centrosome innovation might have been critical during metazoan evolution.
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                Author and article information

                Journal
                J Cell Biol
                J. Cell Biol
                jcb
                jcb
                The Journal of Cell Biology
                The Rockefeller University Press
                0021-9525
                1540-8140
                06 November 2017
                : 216
                : 11
                : 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.

                Author information
                http://orcid.org/0000-0002-9968-1779
                Article
                201610039
                10.1083/jcb.201610039
                5674878
                28993469
                90c198ff-0648-43e5-9463-0d2303c6c392
                © 2017 Pitaval et al.

                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/).

                History
                : 12 October 2016
                : 02 June 2017
                : 17 August 2017
                Funding
                Funded by: European Research Council, DOI http://dx.doi.org/10.13039/100010663;
                Award ID: SpiCy 310472
                Categories
                Research Articles
                Article
                25
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                Cell biology
                Cell biology

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