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.
Mesh Terms:
Actins, Amino Acid Sequence, Animals, Base Sequence, Carrier Proteins, Cattle, Cytoskeletal Proteins, DNA, Complementary, Evolution, Molecular, Humans, Intracellular Signaling Peptides and Proteins, Macromolecular Substances, Microfilaments, 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
Cell
Date: Jul. 23, 2004
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