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Nature Cell Biology 2, 441–448 (1 July 2000) | doi:10.1038/35017080

A complex of N-WASP and WIP integrates signalling cascades that lead to actin polymerization

Violaine Moreau , Friedrich Frischknecht , Inge Reckmann , Renaud Vincentelli , Gw|[eacute]|na|[euml]|l Rabut , Donn Stewart & Michael Way

Wiskott–Aldrich syndrome protein (WASP) and N-WASP have emerged as key proteins connecting signalling cascades to actin polymerization. Here we show that the amino-terminal WH1 domain, and not the polyproline-rich region, of N-WASP is responsible for its recruitment to sites of actin polymerization during Cdc42-independent, actin-based motility of vaccinia virus. Recruitment of N-WASP to vaccinia is mediated by WASP-interacting protein (WIP), whereas in Shigella WIP is recruited by N-WASP. Our observations show that vaccinia and Shigella activate the Arp2/3 complex to achieve actin-based motility, by mimicking either the SH2/SH3-containing adaptor or Cdc42 signalling pathways to recruit the N-WASP–WIP complex. We propose that the N-WASP–WIP complex has a pivotal function in integrating signalling cascades that lead to actin polymerization.