Wiskott-Aldrich syndrome protein, a novel effector for the GTPase CDC42Hs, is implicated in actin polymerization

Cell. 1996 Mar 8;84(5):723-34. doi: 10.1016/s0092-8674(00)81050-8.


The Rho family of GTPases control diverse biological processes, including cell morphology and mitogenesis. We have identified WASP, the protein that is defective in Wiskott-Aldrich syndrome (WAS), as a novel effector for CDC42Hs, but not for the other Rho family members, Rac and Rho. This interaction is dependent on the presence of the G protein-binding domain. Cellular expression of epitope-tagged WASP produces clusters of WASP that are highly enriched in polymerized actin. This clustering is not observed with a C-terminally deleted WASP and is inhibited by coexpression with dominant negative CDC42Hs-N17, but not with dominant negative forms of Rac or Rho. Thus, WASP provides a novel link between CDC42Hs and the actin cytoskeleton, which suggests a molecular mechanism for many of the cellular abnormalities in WAS. The WASP sequence contains two novel domains that are homologous to other proteins involved in action organization.

Publication types

  • Research Support, Non-U.S. Gov't
  • Research Support, U.S. Gov't, P.H.S.

MeSH terms

  • Actins / metabolism*
  • Amino Acid Sequence
  • Animals
  • Binding Sites
  • Cell Cycle Proteins / chemistry
  • Cell Cycle Proteins / isolation & purification
  • Cell Cycle Proteins / metabolism*
  • Cell Line
  • Chlorocebus aethiops
  • Consensus Sequence
  • Cytosol / metabolism
  • GTP Phosphohydrolases / metabolism*
  • GTP-Binding Proteins / chemistry
  • GTP-Binding Proteins / isolation & purification
  • GTP-Binding Proteins / metabolism*
  • Guanosine Diphosphate
  • Guanosine Triphosphate / metabolism
  • Humans
  • Models, Biological
  • Molecular Sequence Data
  • Neutrophils / metabolism
  • Protein Biosynthesis
  • Proteins / chemistry
  • Proteins / metabolism*
  • Recombinant Proteins / biosynthesis
  • Recombinant Proteins / metabolism
  • Sequence Homology, Amino Acid
  • Sequence Tagged Sites
  • Transfection
  • Wiskott-Aldrich Syndrome / genetics*
  • Wiskott-Aldrich Syndrome Protein
  • cdc42 GTP-Binding Protein


  • Actins
  • Cell Cycle Proteins
  • Proteins
  • Recombinant Proteins
  • WAS protein, human
  • Wiskott-Aldrich Syndrome Protein
  • Guanosine Diphosphate
  • Guanosine Triphosphate
  • GTP Phosphohydrolases
  • GTP-Binding Proteins
  • cdc42 GTP-Binding Protein