Nature Cell Biology
3, 484 - 491 (2001)
Published online: 11 April 2001; | doi:10.1038/35074551
WIP regulates N-WASP-mediated actin polymerization and filopodium formationNarcisa Martinez-Quiles1, Rajat Rohatgi2, Inés M. Antón1, Miguel Medina3, Stephen P. Saville1, Hiroaki Miki4, Hideki Yamaguchi4, Tadaomi Takenawa4, John H. Hartwig5, Raif S. Geha1
& Narayanaswamy Ramesh11
Department of Pediatrics, Division of Immunology, Children's Hospital, Harvard Medical School, Boston, Massachusetts 02115, USA
2
Department of Cell Biology, Boston, Massachusetts 02115, USA
3
Department of Neurology, Boston, Massachusetts 02115, USA
4
Department of Biochemistry, Institute of Medical Science, University of Tokyo, 4-6-1 Shirokanedai, Minato-ku, Tokyo 108, Japan
5
Department of Medicine, Division of Experimental Medicine, Brigham and Women's Hospital, Boston, Massachusetts 02115, USA
Correspondence should be addressed to Raif S. Geha raif.geha@tch.harvard.eduInduction of filopodia is dependent on activation of the small GTPase Cdc42 and on neural Wiskott−Aldrich-syndrome protein (N-WASP). Here we show that WASP-interacting protein (WIP) interacts directly with N-WASP and actin. WIP retards N-WASP/Cdc42-activated actin polymerization mediated by the Arp2/3 complex, and stabilizes actin filaments. Microinjection of WIP into NIH 3T3 fibroblasts induces filopodia; this is inhibited by microinjection of anti-N-WASP antibody. Microinjection of anti-WIP antibody inhibits induction of filopodia by bradykinin, by an active Cdc42 mutant (Cdc42(V12)) and by N-WASP. Our results indicate that WIP and N-WASP may act as a functional unit in filopodium formation, which is consistent with their role in actin-tail formation in cells infected with vaccinia virus or Shigella.
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