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      Cep164 mediates vesicular docking to the mother centriole during early steps of ciliogenesis

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          Abstract

          Cep164 provides a molecular link between the mother centriole and the ciliary membrane biogenesis machinery by interacting with the GEF Rabin8 and the GTPase Rab8.

          Abstract

          Cilia formation is a multi-step process that starts with the docking of a vesicle at the distal part of the mother centriole. This step marks the conversion of the mother centriole into the basal body, from which axonemal microtubules extend to form the ciliary compartment. How vesicles are stably attached to the mother centriole to initiate ciliary membrane biogenesis is unknown. Here, we investigate the molecular role of the mother centriolar component Cep164 in ciliogenesis. We show that Cep164 was indispensable for the docking of vesicles at the mother centriole. Using biochemical and functional assays, we identified the components of the vesicular transport machinery, the GEF Rabin8 and the GTPase Rab8, as interacting partners of Cep164. We propose that Cep164 is targeted to the apical domain of the mother centriole to provide the molecular link between the mother centriole and the membrane biogenesis machinery that initiates cilia formation.

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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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            Getting started with yeast.

            F. Sherman (1991)
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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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                Author and article information

                Journal
                J Cell Biol
                J. Cell Biol
                jcb
                The Journal of Cell Biology
                The Rockefeller University Press
                0021-9525
                1540-8140
                24 December 2012
                : 199
                : 7
                : 1083-1101
                Affiliations
                [1 ]DKFZ-ZMBH Alliance, German Cancer Research Center, 69120 Heidelberg, Germany
                [2 ]DKFZ-ZMBH Alliance, Center for Molecular and Cellular Biology, 69120 Heidelberg, Germany
                [3 ]Department of Tumor Virology, German Cancer Research Center, 69120 Heidelberg, Germany
                Author notes
                Correspondence to Gislene Pereira: g.pereira@ 123456dkfz.de
                Article
                201202126
                10.1083/jcb.201202126
                3529528
                23253480
                ae9c5e52-602b-4259-bd69-ca9301d215c9
                © 2012 Schmidt 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 3.0 Unported license, as described at http://creativecommons.org/licenses/by-nc-sa/3.0/).

                History
                : 23 February 2012
                : 26 November 2012
                Categories
                Research Articles
                Article

                Cell biology
                Cell biology

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