Tubulin nucleotide status controls Sas-4-dependent pericentriolar material recruitment

Nat Cell Biol. 2012 Aug;14(8):865-73. doi: 10.1038/ncb2527. Epub 2012 Jun 24.

Abstract

Regulated centrosome biogenesis is required for accurate cell division and for maintaining genome integrity. Centrosomes consist of a centriole pair surrounded by a protein network known as pericentriolar material (PCM). PCM assembly is a tightly regulated, critical step that determines the size and capability of centrosomes. Here, we report a role for tubulin in regulating PCM recruitment through the conserved centrosomal protein Sas-4. Tubulin directly binds to Sas-4; together they are components of cytoplasmic complexes of centrosomal proteins. A Sas-4 mutant, which cannot bind tubulin, enhances centrosomal protein complex formation and has abnormally large centrosomes with excessive activity. These results suggest that tubulin negatively regulates PCM recruitment. Whereas tubulin-GTP prevents Sas-4 from forming protein complexes, tubulin-GDP promotes it. Thus, the regulation of PCM recruitment by tubulin depends on its GTP/GDP-bound state. These results identify a role for tubulin in regulating PCM recruitment independent of its well-known role as a building block of microtubules. On the basis of its guanine-bound state, tubulin can act as a molecular switch in PCM recruitment.

Publication types

  • Research Support, N.I.H., Extramural

MeSH terms

  • Animals
  • Animals, Genetically Modified
  • Blotting, Western
  • Centrioles
  • Centrosome / metabolism*
  • Drosophila / genetics
  • Drosophila / metabolism*
  • Drosophila Proteins / genetics
  • Drosophila Proteins / metabolism*
  • Fluorescent Antibody Technique
  • Genes, Switch
  • Microtubule-Associated Proteins
  • Nucleotides / chemistry
  • Nucleotides / genetics
  • Organ Size
  • Protein Binding
  • Tubulin / genetics*
  • Tubulin / metabolism*

Substances

  • Drosophila Proteins
  • Microtubule-Associated Proteins
  • Nucleotides
  • Sas-4 protein, Drosophila
  • Tubulin