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

Hsin-Yi Henry Ho, Rajat Rohatgi, Andres M. Lebensohn, Ma Le Ma, Jiaxu Li, Steven P. Gygi, Marc W. Kirschner

Research output: Contribution to journalArticle

323 Scopus citations

Abstract

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.

Original languageEnglish (US)
Pages (from-to)203-216
Number of pages14
JournalCell
Volume118
Issue number2
DOIs
StatePublished - Jul 23 2004
Externally publishedYes

ASJC Scopus subject areas

  • Cell Biology
  • Molecular Biology

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    Ho, H-Y. H., Rohatgi, R., Lebensohn, A. M., Le Ma, M., Li, J., Gygi, S. P., & Kirschner, M. W. (2004). Toca-1 mediates Cdc42-dependent actin nucleation by activating the N-WASP-WIP complex. Cell, 118(2), 203-216. https://doi.org/10.1016/j.cell.2004.06.027