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 RIS Download
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