title: Casein kinase 1δ functions at the centrosome and Golgi to promote ciliogenesis.
abstract: Inhibition of casein kinase 1 delta (CK1δ) blocks primary ciliogenesis in human telomerase reverse transcriptase immortalized retinal pigmented epithelial and mouse inner medullary collecting duct cells-3. Mouse embryonic fibroblasts (MEFs) and retinal cells from Csnk1d (CK1δ)-null mice also exhibit ciliogenesis defects. CK1δ catalytic activity and centrosomal localization signal (CLS) are required to rescue cilia formation in MEFs(Csnk1d null). Furthermore, expression of a truncated derivative containing the CLS displaces full-length CK1δ from the centrosome and decreases ciliary length in control MEFs, suggesting that centrosomal CK1δ has a role in ciliogenesis. CK1δ inhibition also alters pericentrosomal or ciliary distribution of several proteins involved in ciliary transport, including Ras-like in rat brain-11A, Ras-like in rat brain-8A, centrosomal protein of 290 kDa, pericentriolar material protein 1, and polycystin-2, as well as the Golgi distribution of its binding partner, A-kinase anchor protein 450 (AKAP450). As reported for AKAP450, CK1δ was required for microtubule nucleation at the Golgi and maintenance of Golgi integrity. Overexpression of an AKAP450 fragment containing the CK1δ-binding site inhibits Golgi-derived microtubule nucleation, Golgi distribution of intraflagellar transport protein 20 homologue, and ciliogenesis. Our results suggest that CK1δ mediates primary ciliogenesis by multiple mechanisms, one involving its centrosomal function and another dependent on its interaction with AKAP450 at the Golgi, where it is important for maintaining Golgi organization and polarized trafficking of multiple factors that mediate ciliary transport.
authors.affiliation: Laboratory of Cellular and Molecular Biology, National Cancer Institute, Bethesda, MD 20892.
authors.forename: Yoshimi Endo
authors.initials: YE
authors.lastname: Greer
authors.affiliation: Laboratory of Cell and Developmental Signaling, National Cancer Institute, Frederick, MD 21702.
authors.forename: Christopher J
authors.initials: CJ
authors.lastname: Westlake
authors.affiliation: Genetic Disease Research Branch, National Human Genome Research Institute, Bethesda, MD 20892.
authors.forename: Bo
authors.initials: B
authors.lastname: Gao
authors.affiliation: Ophthalmic Genetics and Visual Function Branch, National Eye Institute, Bethesda, MD 20892.
authors.forename: Kapil
authors.initials: K
authors.lastname: Bharti
authors.affiliation: Laboratory of Cellular and Molecular Biology, National Cancer Institute, Bethesda, MD 20892.
authors.forename: Yoko
authors.initials: Y
authors.lastname: Shiba
authors.affiliation: Laboratory of Cellular and Molecular Biology, National Cancer Institute, Bethesda, MD 20892.
authors.forename: Charles P
authors.initials: CP
authors.lastname: Xavier
authors.affiliation: Program in Molecular Medicine, University of Massachusetts Medical School, Worcester, MA 01605.
authors.forename: Gregory J
authors.initials: GJ
authors.lastname: Pazour
authors.affiliation: Genetic Disease Research Branch, National Human Genome Research Institute, Bethesda, MD 20892.
authors.forename: Yingzi
authors.initials: Y
authors.lastname: Yang
authors.affiliation: Laboratory of Cellular and Molecular Biology, National Cancer Institute, Bethesda, MD 20892 rubinj@mail.nih.gov.
authors.forename: Jeffrey S
authors.initials: JS
authors.lastname: Rubin
mesh_terms: D054758:A Kinase Anchor Proteins / Q000096:biosynthesis / Q000378:metabolism*; D000818:Animals; D000951:Antigens, Neoplasm; D001665:Binding Sites; D002352:Carrier Proteins; D048148:Casein Kinase Idelta / Q000037:antagonists & inhibitors* / Q000235:genetics; D018797:Cell Cycle Proteins / Q000378:metabolism; D002460:Cell Line; D018385:Centrosome / Q000378:metabolism*; D002923:Cilia / Q000378:metabolism*; D003598:Cytoskeletal Proteins; D006056:Golgi Apparatus / Q000378:metabolism*; D006801:Humans; D051379:Mice; D018345:Mice, Knockout; D008869:Microtubule-Associated Proteins / Q000096:biosynthesis / Q000378:metabolism*; D008870:Microtubules / Q000378:metabolism; D009687:Nuclear Proteins / Q000378:metabolism; D021381:Protein Transport; D034622:RNA Interference; D034741:RNA, Small Interfering; D012160:Retina / Q000166:cytology; D015398:Signal Transduction / Q000235:genetics; D050396:TRPP Cation Channels / Q000378:metabolism; D019098:Telomerase / Q000235:genetics; D020691:rab GTP-Binding Proteins / Q000378:metabolism; D000099193:rab11 GTP-Binding Proteins
chemical_list: D054758:A Kinase Anchor Proteins; D000951:Antigens, Neoplasm; D002352:Carrier Proteins; D048148:Casein Kinase Idelta; D018797:Cell Cycle Proteins; D003598:Cytoskeletal Proteins; D008869:Microtubule-Associated Proteins; D009687:Nuclear Proteins; D034741:RNA, Small Interfering; D050396:TRPP Cation Channels; D019098:Telomerase; D020691:rab GTP-Binding Proteins; D000099193:rab11 GTP-Binding Proteins; C464931:Akap9 protein, mouse; C513600:Cep290 protein, mouse; C514104:Ift20 protein, mouse; C490114:Pcm1 protein, mouse; C546061:Rab8a protein, mouse