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

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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

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Actins
Nucleation
Actin-Related Protein 2-3 Complex
Wiskott-Aldrich Syndrome
rho GTP-Binding Proteins
Transducers
Actin Cytoskeleton
Polymerization
GTP Phosphohydrolases
Purification
Proteins

ASJC Scopus subject areas

  • Cell Biology
  • Molecular Biology

Cite this

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

Toca-1 mediates Cdc42-dependent actin nucleation by activating the N-WASP-WIP complex. / Ho, Hsin-Yi Henry; Rohatgi, Rajat; Lebensohn, Andres M.; Le Ma, Ma; Li, Jiaxu; Gygi, Steven P.; Kirschner, Marc W.

In: Cell, Vol. 118, No. 2, 23.07.2004, p. 203-216.

Research output: Contribution to journalArticle

Ho, H-YH, Rohatgi, R, Lebensohn, AM, Le Ma, M, Li, J, Gygi, SP & Kirschner, MW 2004, 'Toca-1 mediates Cdc42-dependent actin nucleation by activating the N-WASP-WIP complex', Cell, vol. 118, no. 2, pp. 203-216. https://doi.org/10.1016/j.cell.2004.06.027
Ho, Hsin-Yi Henry ; Rohatgi, Rajat ; Lebensohn, Andres M. ; Le Ma, Ma ; Li, Jiaxu ; Gygi, Steven P. ; Kirschner, Marc W. / Toca-1 mediates Cdc42-dependent actin nucleation by activating the N-WASP-WIP complex. In: Cell. 2004 ; Vol. 118, No. 2. pp. 203-216.
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