title: A centrosome interactome provides insight into organelle assembly and reveals a non-duplication role for Plk4.
abstract: The centrosome is the major microtubule-organizing centre of many cells, best known for its role in mitotic spindle organization. How the proteins of the centrosome are accurately assembled to carry out its many functions remains poorly understood. The non-membrane-bound nature of the centrosome dictates that protein-protein interactions drive its assembly and functions. To investigate this massive macromolecular organelle, we generated a 'domain-level' centrosome interactome using direct protein-protein interaction data from a focused yeast two-hybrid screen. We then used biochemistry, cell biology and the model organism Drosophila to provide insight into the protein organization and kinase regulatory machinery required for centrosome assembly. Finally, we identified a novel role for Plk4, the master regulator of centriole duplication. We show that Plk4 phosphorylates Cep135 to properly position the essential centriole component Asterless. This interaction landscape affords a critical framework for research of normal and aberrant centrosomes.
authors: Cell Biology and Physiology Center, National Heart, Lung, and Blood Institute, National Institutes of Health, Bethesda, Maryland 20892, USA.
authors: Brian J
authors: BJ
authors: Galletta
authors: Cell Biology and Physiology Center, National Heart, Lung, and Blood Institute, National Institutes of Health, Bethesda, Maryland 20892, USA.
authors: Carey J
authors: CJ
authors: Fagerstrom
authors: Cell Biology and Physiology Center, National Heart, Lung, and Blood Institute, National Institutes of Health, Bethesda, Maryland 20892, USA.
authors: Todd A
authors: TA
authors: Schoborg
authors: Department of Cellular and Molecular Medicine, University of Arizona Cancer Center, University of Arizona, Tucson, Arizona 85724, USA.
authors: Tiffany A
authors: TA
authors: McLamarrah
authors: Department of Cellular and Molecular Medicine, University of Arizona Cancer Center, University of Arizona, Tucson, Arizona 85724, USA.
authors: John M
authors: JM
authors: Ryniawec
authors: Department of Cellular and Molecular Medicine, University of Arizona Cancer Center, University of Arizona, Tucson, Arizona 85724, USA.
authors: Daniel W
authors: DW
authors: Buster
authors: Department of Biology, University of North Carolina at Chapel Hill, Chapel Hill, North Carolina 27599, USA.
authors: Kevin C
authors: KC
authors: Slep
authors: Department of Cellular and Molecular Medicine, University of Arizona Cancer Center, University of Arizona, Tucson, Arizona 85724, USA.
authors: Gregory C
authors: GC
authors: Rogers
authors: Cell Biology and Physiology Center, National Heart, Lung, and Blood Institute, National Institutes of Health, Bethesda, Maryland 20892, USA.
authors: Nasser M
authors: NM
authors: Rusan
mesh_terms: D000595:Amino Acid Sequence; D000818:Animals; D018797:Cell Cycle Proteins / Q000737:chemistry / Q000378:metabolism; D018385:Centrosome / Q000378:metabolism*; D029721:Drosophila Proteins / Q000378:metabolism*; D004331:Drosophila melanogaster / Q000378:metabolism*; D020440:Gene Duplication; D015388:Organelles / Q000378:metabolism*; D010766:Phosphorylation; D011485:Protein Binding; D060066:Protein Interaction Maps; D055503:Protein Multimerization; D017346:Protein Serine-Threonine Kinases / Q000378:metabolism*; D013379:Substrate Specificity
chemical_list: D018797:Cell Cycle Proteins; D029721:Drosophila Proteins; D017346:Protein Serine-Threonine Kinases; C522064:Sak protein, Drosophila