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WAVE, a novel WASP‐family protein involved in actin reorganization induced by Rac

Hiroaki Miki, Shiro Suetsugu, Tadaomi Takenawa

Author Affiliations

  1. Hiroaki Miki1,
  2. Shiro Suetsugu1 and
  3. Tadaomi Takenawa*,1
  1. 1 Department of Biochemistry, Institute of Medical Science, University of Tokyo, 4‐6‐1 Shirokanedai, Minato‐ku, Tokyo, 108, Japan
  1. *Corresponding author. E-mail: takenawa{at}ims.u-tokyo.ac.jp
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Abstract

Rac is a Rho‐family small GTPase that induces the formation of membrane ruffles. However, it is poorly understood how Rac‐induced reorganization of the actin cytoskeleton, which is essential for ruffle formation, is regulated. Here we identify a novel Wiskott–Aldrich syndrome protein (WASP)‐family protein, WASP family Verprolin‐homologous protein (WAVE), as a regulator of actin reorganization downstream of Rac. Ectopically expressed WAVE induces the formation of actin filament clusters that overlap with the expressed WAVE itself. In this actin clustering, profilin, a monomeric actin‐binding protein that has been suggested to be involved in actin polymerization, was shown to be essential. The expression of a dominant‐active Rac mutant induces the translocation of endogenous WAVE from the cytosol to membrane ruffling areas. Furthermore, the co‐expression of a ΔVPH WAVE mutant that cannot induce actin reorganization specifically suppresses the ruffle formation induced by Rac, but has no effect on Cdc42‐induced actin‐microspike formation, a phenomenon that is also known to be dependent on rapid actin reorganization. The ΔVPH WAVE also suppresses membrane‐ruffling formation induced by platelet‐derived growth factor in Swiss 3T3 cells. Taken together, we conclude that WAVE plays a critical role downstream of Rac in regulating the actin cytoskeleton required for membrane ruffling.

  • Received April 17, 1998.
  • Revision received October 1, 1998.
  • Accepted October 2, 1998.
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