guanosine-diphosphate and Wiskott-Aldrich-Syndrome

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.

Topics: Actins; Amino Acid Sequence; Animals; Binding Sites; cdc42 GTP-Binding Protein; Cell Cycle Proteins; Cell Line; Chlorocebus aethiops; Consensus Sequence; Cytosol; GTP Phosphohydrolases; GTP-Binding Proteins; Guanosine Diphosphate; Guanosine Triphosphate; Humans; Models, Biological; Molecular Sequence Data; Neutrophils; Protein Biosynthesis; Proteins; Recombinant Proteins; Sequence Homology, Amino Acid; Sequence Tagged Sites; Transfection; Wiskott-Aldrich Syndrome; Wiskott-Aldrich Syndrome Protein