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      Cilium structure, assembly, and disassembly regulated by the cytoskeleton

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          Abstract

          The cilium, once considered a vestigial structure, is a conserved, microtubule-based organelle critical for transducing extracellular chemical and mechanical signals that control cell polarity, differentiation, and proliferation. The cilium undergoes cycles of assembly and disassembly that are controlled by complex inter-relationships with the cytoskeleton. Microtubules form the core of the cilium, the axoneme, and are regulated by post-translational modifications, associated proteins, and microtubule dynamics. Although actin and septin cytoskeletons are not major components of the axoneme, they also regulate cilium organization and assembly state. Here, we discuss recent advances on how these different cytoskeletal systems­ affect cilium function, structure, and organization.

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          Most cited references151

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          HDAC6 modulates cell motility by altering the acetylation level of cortactin.

          Histone deacetylase 6 (HDAC6) is a tubulin-specific deacetylase that regulates microtubule-dependent cell movement. In this study, we identify the F-actin-binding protein cortactin as a HDAC6 substrate. We demonstrate that HDAC6 binds cortactin and that overexpression of HDAC6 leads to hypoacetylation of cortactin, whereas inhibition of HDAC6 activity leads to cortactin hyperacetylation. HDAC6 alters the ability of cortactin to bind F-actin by modulating a "charge patch" in its repeat region. Introduction of charge-preserving or charge-neutralizing mutations in this cortactin repeat region correlates with the gain or loss of F-actin binding ability, respectively. Cells expressing a charge-neutralizing cortactin mutant were less motile than control cells or cells expressing a charge-preserving mutant. These findings suggest that, in addition to its role in microtubule-dependent cell motility, HDAC6 influences actin-dependent cell motility by altering the acetylation status of cortactin, which, in turn, changes the F-actin binding activity of cortactin.
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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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              Mechanisms of mechanotransduction.

              Essentially all organisms from bacteria to humans are mechanosensitive. Physical forces regulate a large array of physiological processes, and dysregulation of mechanical responses contributes to major human diseases. A survey of both specialized and widely expressed mechanosensitive systems suggests that physical forces provide a general means of altering protein conformation to generate signals. Specialized systems differ mainly in having acquired efficient mechanisms for transferring forces to the mechanotransducers.
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                Author and article information

                Journal
                Biochem J
                Biochem. J
                ppbiochemj
                BCJ
                Biochemical Journal
                Portland Press Ltd.
                0264-6021
                1470-8728
                31 July 2018
                31 July 2018
                : 475
                : 14
                : 2329-2353
                Affiliations
                [1 ]Department of Molecular and Cellular Physiology, Stanford University, Stanford, CA 94305, U.S.A.
                [2 ]Department of Biology, Stanford University, Stanford, CA 94305, U.S.A.
                [3 ]Department of Genetics, Stanford University, Stanford, CA 94305, U.S.A.
                Author notes
                Correspondence: W. James Nelson ( wjnelson@ 123456stanford.edu )
                [*]

                Correspondence after publication: mmirvis@ 123456stanford.edu .

                Article
                BCJ-475-2329
                10.1042/BCJ20170453
                6068341
                30064990
                88298e0c-03b3-4d23-90d9-130d86197982
                © 2018 The Author(s)

                This is an open access article published by Portland Press Limited on behalf of the Biochemical Society and distributed under the Creative Commons Attribution License 4.0 (CC BY-NC-ND).

                History
                : 22 March 2018
                : 2 July 2018
                : 4 July 2018
                Categories
                Review Articles
                Review Article
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                Biochemistry
                actin,cilia,cytoskeleton,microtubule,organelle biogenesis,signaling
                Biochemistry
                actin, cilia, cytoskeleton, microtubule, organelle biogenesis, signaling

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