Nature Cell Biology
2, 441 - 448 (2000)
Published online: 16 June 2000; | doi:10.1038/35017080
A complex of N-WASP and WIP integrates signalling cascades that lead
to actin polymerizationViolaine Moreau1, 2, 4, Friedrich Frischknecht1, 4, Inge Reckmann1, Renaud Vincentelli1, Gwénaël Rabut1, Donn Stewart3
& Michael Way1
European Molecular Biology Laboratory,
Meyerhofstrasse 1, 69117 Heidelberg,
Germany
2
Current address: Laboratoire des Facteurs de Croissance
et de la Differenciation Cellulaire, Universite Bordeaux I,
Avenue des facultes, 33405 Talence, France
3
National Cancer Institute, National Institutes of Health, 9000 Rockville Pike, Bethesda, Maryland 20892, USA
Correspondence should be addressed to Michael Way Way@EMBL-Heidelberg.de4
These authors contributed equally to this work 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.
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