title: Proximity interactions among centrosome components identify regulators of centriole duplication.
abstract: The centrosome consists of a pair of centrioles and surrounding pericentriolar material (PCM). Many vertebrate cells also have an array of granules, termed centriolar satellites, that localize around the centrosome and are associated with centrosome and cilium function. Centriole duplication occurs once per cell cycle and is effected by a set of proteins including PLK4, CEP192, CEP152, CEP63, and CPAP. Information on the relationships between these components is limited due to the difficulty in assaying interactions in the context of the centrosome. Here, we used proximity-dependent biotin identification (BioID) to identify proximity interactions among centriole duplication proteins. PLK4, CEP192, and CEP152 BioID identified known physically interacting proteins and a new interaction between CEP152 and CDK5RAP2 consistent with a function of CEP152 in PCM recruitment. BioID for CEP63 and its paralog CCDC67 revealed extensive proximity interactions with centriolar satellite proteins. Focusing on these satellite proteins identified two new regulators of centriole duplication, CCDC14 and KIAA0753. Both proteins colocalize with CEP63 to satellites, bind to CEP63, and identify other satellite proteins by BioID. KIAA0753 positively regulates centriole duplication and CEP63 centrosome localization, whereas CCDC14 negatively regulates both processes. These results suggest that centriolar satellites have a previously unappreciated function in regulating centriole duplication.
authors.affiliation: Department of Biology, Stanford University, Stanford, CA 94305-5020, USA.
authors.forename: Elif Nur
authors.initials: EN
authors.lastname: Firat-Karalar
authors.affiliation: Department of Chemical Biology, The Scripps Research Institute, 10550 North Torrey Pines Road, 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 North Torrey Pines Road, La Jolla, CA 92037, USA.
authors.forename: John R
authors.initials: JR
authors.lastname: Yates
authors.affiliation: Department of Biology, Stanford University, Stanford, CA 94305-5020, USA; Department of Genetics, Stanford School of Medicine, Stanford, CA 94305-5120, USA. Electronic address: stearns@stanford.edu.
authors.forename: Tim
authors.initials: T
authors.lastname: Stearns
mesh_terms: D001710:Biotin / Q000378:metabolism; D019921:Biotinylation; D018797:Cell Cycle Proteins / Q000502:physiology; D002460:Cell Line; D002502:Centrioles / Q000502:physiology*; D018385:Centrosome / Q000502:physiology*; D002868:Chromosomal Proteins, Non-Histone / Q000502:physiology; D006801:Humans; D047908:Intracellular Signaling Peptides and Proteins / Q000502:physiology; D008869:Microtubule-Associated Proteins / Q000502:physiology; D015778:Minor Histocompatibility Antigens / Q000502:physiology; D009419:Nerve Tissue Proteins / Q000502:physiology; D017346:Protein Serine-Threonine Kinases / Q000502:physiology
chemical_list: C405929:CDK5RAP2 protein, human; C414735:CENPJ protein, human; C551028:CEP152 protein, human; D018797:Cell Cycle Proteins; C526596:Cep192 protein, human; D002868:Chromosomal Proteins, Non-Histone; D047908:Intracellular Signaling Peptides and Proteins; D008869:Microtubule-Associated Proteins; D015778:Minor Histocompatibility Antigens; D009419:Nerve Tissue Proteins; D001710:Biotin; C490219:PLK4 protein, human; D017346:Protein Serine-Threonine Kinases