title: SAS-6 defines a protein family required for centrosome duplication in C. elegans and in human cells.
abstract: The mechanisms that ensure centrosome duplication are poorly understood. In Caenorhabditis elegans, ZYG-1, SAS-4, SAS-5 and SPD-2 are required for centriole formation. However, it is unclear whether these proteins have functional homologues in other organisms. Here, we identify SAS-6 as a component that is required for daughter centriole formation in C. elegans. SAS-6 is a coiled-coil protein that is recruited to centrioles at the onset of the centrosome duplication cycle. Our analysis indicates that SAS-6 and SAS-5 associate and that this interaction, as well as ZYG-1 function, is required for SAS-6 centriolar recruitment. SAS-6 is the founding member of an evolutionarily conserved protein family that contains the novel PISA motif. We investigated the function of the human homologue of SAS-6. GFP-HsSAS-6 localizes to centrosomes and its overexpression results in excess foci-bearing centriolar markers. Furthermore, siRNA-mediated inactivation of HsSAS-6 in U2OS cells abrogates centrosome overduplication following aphidicolin treatment and interferes with the normal centrosome duplication cycle. Therefore, HsSAS-6 is also required for centrosome duplication, indicating that the function of SAS-6-related proteins has been widely conserved during evolution.
authors.affiliation: Swiss Institute for Experimental Cancer Research (ISREC), CH-1066 Epalinges/Lausanne, Switzerland.
authors.forename: Sebastian
authors.initials: S
authors.lastname: Leidel
authors.forename: Marie
authors.initials: M
authors.lastname: Delattre
authors.forename: Lorenzo
authors.initials: L
authors.lastname: Cerutti
authors.forename: Karine
authors.initials: K
authors.lastname: Baumer
authors.forename: Pierre
authors.initials: P
authors.lastname: Gönczy
mesh_terms: D000595:Amino Acid Sequence; D000818:Animals; D016590:Aphidicolin / Q000494:pharmacology; D017173:Caenorhabditis elegans / Q000378:metabolism*; D029742:Caenorhabditis elegans Proteins / Q000502:physiology*; D018797:Cell Cycle Proteins / Q000502:physiology*; D002502:Centrioles / Q000502:physiology*; D018385:Centrosome / Q000502:physiology*; D017124:Conserved Sequence; D006801:Humans; D008565:Membrane Proteins / Q000378:metabolism; D008969:Molecular Sequence Data; D016415:Sequence Alignment; D059470:Tetraspanins
chemical_list: D029742:Caenorhabditis elegans Proteins; D018797:Cell Cycle Proteins; D008565:Membrane Proteins; C488496:SAS-5 protein, C elegans; C497201:SAS-6 protein, C elegans; C497202:SASS6 protein, human; C086385:TSPAN31 protein, human; D059470:Tetraspanins; D016590:Aphidicolin