A Complex of N-WASP and WIP Integrates Signalling Cascades That Lead to Actin Polymerization

Nat Cell Biol. 2000 Jul;2(7):441-8. doi: 10.1038/35017080.

Abstract

Wiskott-Aldrich syndrome protein (WASP) and N-WASP have emerged as key proteins connecting signalling cascades to actin polymerization. Here we show that the amino-terminal WH1 domain, and not the polyproline-rich region, of N-WASP is responsible for its recruitment to sites of actin polymerization during Cdc42-independent, actin-based motility of vaccinia virus. Recruitment of N-WASP to vaccinia is mediated by WASP-interacting protein (WIP), whereas in Shigella WIP is recruited by N-WASP. Our observations show that vaccinia and Shigella activate the Arp2/3 complex to achieve actin-based motility, by mimicking either the SH2/SH3-containing adaptor or Cdc42 signalling pathways to recruit the N-WASP-WIP complex. We propose that the N-WASP-WIP complex has a pivotal function in integrating signalling cascades that lead to actin polymerization.

MeSH terms

  • Actin Cytoskeleton / chemistry
  • Actin Cytoskeleton / metabolism*
  • Actins / metabolism*
  • Adaptor Proteins, Signal Transducing
  • Amino Acid Motifs
  • Biopolymers / chemistry
  • Biopolymers / metabolism
  • Carrier Proteins / genetics
  • Carrier Proteins / metabolism*
  • Cytoskeletal Proteins
  • Fluorescent Antibody Technique
  • HeLa Cells
  • Humans
  • Intracellular Signaling Peptides and Proteins
  • Movement
  • Mutation / genetics
  • Nerve Tissue Proteins / chemistry
  • Nerve Tissue Proteins / genetics
  • Nerve Tissue Proteins / metabolism*
  • Oncogene Proteins / genetics
  • Oncogene Proteins / metabolism
  • Phosphorylation
  • Phosphotyrosine / metabolism
  • Protein Binding
  • Recombinant Fusion Proteins / chemistry
  • Recombinant Fusion Proteins / genetics
  • Recombinant Fusion Proteins / metabolism
  • Shigella / physiology
  • Signal Transduction*
  • Vaccinia virus / physiology
  • Wiskott-Aldrich Syndrome / genetics
  • Wiskott-Aldrich Syndrome Protein, Neuronal
  • cdc42 GTP-Binding Protein / genetics
  • cdc42 GTP-Binding Protein / metabolism
  • src Homology Domains

Substances

  • Actins
  • Adaptor Proteins, Signal Transducing
  • Biopolymers
  • Carrier Proteins
  • Cytoskeletal Proteins
  • Intracellular Signaling Peptides and Proteins
  • Nck protein
  • Nerve Tissue Proteins
  • Oncogene Proteins
  • Recombinant Fusion Proteins
  • WASL protein, human
  • WIPF1 protein, human
  • Wiskott-Aldrich Syndrome Protein, Neuronal
  • Phosphotyrosine
  • cdc42 GTP-Binding Protein