title: The centriolar satellite protein CCDC66 interacts with CEP290 and functions in cilium formation and trafficking.
abstract: Centriolar satellites are membrane-less structures that localize and move around the centrosome and cilium complex in a microtubule-dependent manner. They play important roles in centrosome- and cilium-related processes, including protein trafficking to the centrosome and cilium complex, and ciliogenesis, and they are implicated in ciliopathies. Despite the important regulatory roles of centriolar satellites in the assembly and function of the centrosome and cilium complex, the molecular mechanisms of their functions remain poorly understood. To dissect the mechanism for their regulatory roles during ciliogenesis, we performed an analysis to determine the proteins that localize in close proximity to the satellite protein CEP72, among which was the retinal degeneration gene product CCDC66. We identified CCDC66 as a microtubule-associated protein that dynamically localizes to the centrosome, centriolar satellites and the primary cilium throughout the cell cycle. Like the BBSome component BBS4, CCDC66 distributes between satellites and the primary cilium during ciliogenesis. CCDC66 has extensive proximity interactions with centrosome and centriolar satellite proteins, and co-immunoprecipitation experiments revealed interactions between CCDC66, CEP290 and PCM1. Ciliogenesis, ciliary recruitment of BBS4 and centriolar satellite organization are impaired in cells depleted for CCDC66. Taken together, our findings identify CCDC66 as a targeting factor for centrosome and cilium proteins.
authors.affiliation: Department of Molecular Biology and Genetics, Koç University, Istanbul 34450, Turkey.
authors.forename: Deniz
authors.initials: D
authors.lastname: Conkar
authors.affiliation: Department of Molecular Biology and Genetics, Koç University, Istanbul 34450, Turkey.
authors.forename: Efraim
authors.initials: E
authors.lastname: Culfa
authors.affiliation: Department of Molecular Biology and Genetics, Koç University, Istanbul 34450, Turkey.
authors.forename: Ezgi
authors.initials: E
authors.lastname: Odabasi
authors.affiliation: Department of Chemical Biology, The Scripps Research Institute, 10550 N. Torrey Pines Rd., La Jolla, CA 92037, USA.
authors.forename: Navin
authors.initials: N
authors.lastname: Rauniyar
authors.affiliation: Department of Chemical Biology, The Scripps Research Institute, 10550 N. Torrey Pines Rd., La Jolla, CA 92037, USA.
authors.forename: John R
authors.initials: JR
authors.lastname: Yates
authors.affiliation: Department of Molecular Biology and Genetics, Koç University, Istanbul 34450, Turkey ekaralar@ku.edu.tr.
authors.forename: Elif N
authors.identifier: 0000-0001-7589-473X
authors.initials: EN
authors.lastname: Firat-Karalar
mesh_terms: D002454:Cell Differentiation / Q000235:genetics; D002465:Cell Movement; D002502:Centrioles / Q000276:immunology / Q000378:metabolism*; D018385:Centrosome / Q000502:physiology*; D002923:Cilia / Q000502:physiology*; D005136:Eye Proteins / Q000235:genetics / Q000378:metabolism*; D057809:HEK293 Cells; D006801:Humans; D008869:Microtubule-Associated Proteins / Q000235:genetics / Q000378:metabolism*; D008870:Microtubules / Q000378:metabolism*; D009024:Morphogenesis / Q000235:genetics; D021381:Protein Transport; D011506:Proteins / Q000378:metabolism; D034741:RNA, Small Interfering / Q000235:genetics
chemical_list: C429655:BBS4 protein, human; C000618179:CCDC66 protein, human; C542475:CEP72 protein, human; D005136:Eye Proteins; D008869:Microtubule-Associated Proteins; D011506:Proteins; D034741:RNA, Small Interfering
keywords: BBS4; BioID proximity mapping; CCDC66; Centriolar satellites; Centrosome; Ciliogenesis