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Published online 5 February 2001. doi:10.1083/jcb.152.3.471
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© The Rockefeller University Press, 0021-9525/2001//471 $5.00
The Journal of Cell Biology, Volume 152, Number 3, , 2001 471-482

Original Article

A Novel Neural Wiskott-Aldrich Syndrome Protein (N-Wasp) Binding Protein, Wish, Induces Arp2/3 Complex Activation Independent of Cdc42



Maiko Fukuokaa,b, Shiro Suetsugua, Hiroaki Mikia, Kiyoko Fukamia, Takeshi Endob, and Tadaomi Takenawaa

a Department of Biochemistry, Institute of Medical Science, University of Tokyo, Tokyo 108-8639, Japan
b Department of Biology, Faculty of Science, Chiba University, Chiba 263-8522, Japan
Department of Biochemistry, Institute of Medical Science, University of Tokyo, Shirokanedai, Minatoku, Tokyo 108-8639, Japan.81-3-5449-541781-3-5449-5510

takenawa{at}ims.u-tokyo.ac.jp

We identified a novel adaptor protein that contains a Src homology (SH)3 domain, SH3 binding proline-rich sequences, and a leucine zipper-like motif and termed this protein WASP interacting SH3 protein (WISH). WISH is expressed predominantly in neural tissues and testis. It bound Ash/Grb2 through its proline-rich regions and neural Wiskott-Aldrich syndrome protein (N-WASP) through its SH3 domain. WISH strongly enhanced N-WASP–induced Arp2/3 complex activation independent of Cdc42 in vitro, resulting in rapid actin polymerization. Furthermore, coexpression of WISH and N-WASP induced marked formation of microspikes in Cos7 cells, even in the absence of stimuli. An N-WASP mutant (H208D) that cannot bind Cdc42 still induced microspike formation when coexpressed with WISH. We also examined the contribution of WISH to a rapid actin polymerization induced by brain extract in vitro. Arp2/3 complex was essential for brain extract–induced rapid actin polymerization. Addition of WISH to extracts increased actin polymerization as Cdc42 did. However, WISH unexpectedly could activate actin polymerization even in N-WASP–depleted extracts. These findings suggest that WISH activates Arp2/3 complex through N-WASP–dependent and –independent pathways without Cdc42, resulting in the rapid actin polymerization required for microspike formation.

Key Words: N-WASP • Arp2/3 complex • Ash/Grb2 • microspike formation

© 2001 The Rockefeller University Press

Abbreviations used in this paper: GBD/CRIB, GTPase-binding domain/Cdc42/Rac interactive binding region; GST, glutathione S-transferase; N-WASP, neural Wiskott-Aldrich syndrome protein; PI 3-kinase, phosphatidylinositol 3-kinase; PIP2, phosphatidylinositol 4,5-bisphosphate; SH, Src homology; VCA, verplorin homology, cofilin homology, and acidic region; WAVE, WASP family verplorin-homologous protein; WISH, WASP interacting SH3 protein.


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