The interaction between N-WASP and the Arp2/3 complex links Cdc42-dependent signals to actin assembly

Cell. 1999 Apr 16;97(2):221-31. doi: 10.1016/s0092-8674(00)80732-1.

Abstract

Although small GTP-binding proteins of the Rho family have been implicated in signaling to the actin cytoskeleton, the exact nature of the linkage has remained obscure. We describe a novel mechanism that links one Rho family member, Cdc42, to actin polymerization. N-WASP, a ubiquitously expressed Cdc42-interacting protein, is required for Cdc42-stimulated actin polymerization in Xenopus egg extracts. The C terminus of N-WASP binds to the Arp2/3 complex and dramatically stimulates its ability to nucleate actin polymerization. Although full-length N-WASP is less effective, its activity can be greatly enhanced by Cdc42 and phosphatidylinositol (4,5) bisphosphate. Therefore, N-WASP and the Arp2/3 complex comprise a core mechanism that directly connects signal transduction pathways to the stimulation of actin polymerization.

Publication types

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

MeSH terms

  • Actin-Related Protein 2
  • Actin-Related Protein 3
  • Actins / metabolism*
  • Animals
  • Biopolymers / metabolism
  • Cattle
  • Cell Cycle Proteins / metabolism*
  • Cytoskeletal Proteins*
  • Female
  • GTP-Binding Proteins / metabolism*
  • In Vitro Techniques
  • Macromolecular Substances
  • Models, Biological
  • Nerve Tissue Proteins / chemistry
  • Nerve Tissue Proteins / genetics
  • Nerve Tissue Proteins / metabolism*
  • Oocytes / metabolism
  • Peptide Fragments / chemistry
  • Peptide Fragments / genetics
  • Peptide Fragments / metabolism
  • Phosphatidylinositol 4,5-Diphosphate / metabolism
  • Rats
  • Recombinant Proteins / chemistry
  • Recombinant Proteins / genetics
  • Recombinant Proteins / metabolism
  • Signal Transduction
  • Wiskott-Aldrich Syndrome Protein, Neuronal
  • Xenopus
  • cdc42 GTP-Binding Protein

Substances

  • Actin-Related Protein 2
  • Actin-Related Protein 3
  • Actins
  • Biopolymers
  • Cell Cycle Proteins
  • Cytoskeletal Proteins
  • Macromolecular Substances
  • Nerve Tissue Proteins
  • Peptide Fragments
  • Phosphatidylinositol 4,5-Diphosphate
  • Recombinant Proteins
  • Wasl protein, rat
  • Wiskott-Aldrich Syndrome Protein, Neuronal
  • GTP-Binding Proteins
  • cdc42 GTP-Binding Protein