SAS-6 defines a protein family required for centrosome duplication in C. elegans and in human cells

Nat Cell Biol. 2005 Feb;7(2):115-25. doi: 10.1038/ncb1220.

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.

MeSH terms

  • 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
  • Tetraspanins

Substances

  • Caenorhabditis elegans Proteins
  • Cell Cycle Proteins
  • Membrane Proteins
  • SAS-5 protein, C elegans
  • SAS-6 protein, C elegans
  • SASS6 protein, human
  • TSPAN31 protein, human
  • Tetraspanins
  • Aphidicolin