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Toca-1 mediates Cdc42-dependent actin nucleation by activating the N-WASP-WIP complex.

An important signaling pathway to the actin cytoskeleton links the Rho family GTPase Cdc42 to the actin-nucleating Arp2/3 complex through N-WASP. Nevertheless, these previously identified components are not sufficient to mediate Cdc42-induced actin polymerization in a physiological context. In this paper, we describe the biochemical purification of Toca-1 (transducer of Cdc42-dependent actin assembly) as an essential component of the Cdc42 pathway. Toca-1 binds both N-WASP and Cdc42 and is a member of the evolutionarily conserved PCH protein family. Toca-1 promotes actin nucleation by activating the N-WASP-WIP/CR16 complex, the predominant form of N-WASP in cells. Thus, the cooperative actions of two distinct Cdc42 effectors, the N-WASP-WIP complex and Toca-1, are required for Cdc42-induced actin assembly. These findings represent a significantly revised view of Cdc42-signaling and shed light on the pathogenesis of Wiskott-Aldrich syndrome.

Pubmed ID: 15260990


  • Ho HY
  • Rohatgi R
  • Lebensohn AM
  • Le Ma
  • Li J
  • Gygi SP
  • Kirschner MW



Publication Data

July 23, 2004

Associated Grants

  • Agency: NIGMS NIH HHS, Id: GM026875-27
  • Agency: NHGRI NIH HHS, Id: HG00041

Mesh Terms

  • Actin Cytoskeleton
  • Actins
  • Amino Acid Sequence
  • Animals
  • Base Sequence
  • Carrier Proteins
  • Cattle
  • Cytoskeletal Proteins
  • DNA, Complementary
  • Evolution, Molecular
  • Humans
  • Intracellular Signaling Peptides and Proteins
  • Macromolecular Substances
  • Molecular Sequence Data
  • Nerve Tissue Proteins
  • Phosphatidylinositol 4,5-Diphosphate
  • Phosphoproteins
  • Phylogeny
  • Protein Binding
  • Signal Transduction
  • Wiskott-Aldrich Syndrome
  • Wiskott-Aldrich Syndrome Protein, Neuronal
  • Xenopus Proteins
  • cdc42 GTP-Binding Protein