SAS-6 defines a protein family required for centrosome duplication in C. elegans and in human cells
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.
- URL: http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=PubMed&dopt=Citation&list_uids=15665853
Keywords: Amino Acid Sequence ; Animals ; Aphidicolin/pharmacology ; Caenorhabditis elegans/*metabolism ; Caenorhabditis elegans Proteins/*physiology ; Cell Cycle Proteins/*physiology ; Centrioles/*physiology ; Centrosome/*physiology ; Conserved Sequence ; Humans ; Membrane Proteins/metabolism ; Molecular Sequence Data ; Sequence Alignment
Swiss Institute for Experimental Cancer Research (ISREC), CH-1066 Epalinges/Lausanne, Switzerland.
Record created on 2006-08-24, modified on 2016-08-08