WAVE, a novel WASP-family protein involved in actin reorganization induced by Rac.
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 deltaVPH 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 deltaVPH 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.
Miki
H
H
Department of Biochemistry, Institute of Medical Science, University of Tokyo, 4-6-1 Shirokanedai, Minato-ku, Tokyo 108, Japan.
Suetsugu
S
S
Takenawa
T
T
D016475:3T3 Cells; D000199:Actins / Q000378:metabolism*; D000595:Amino Acid Sequence; D000818:Animals; D019556:COS Cells; D003285:Contractile Proteins; D005656:Fungal Proteins / Q000737:chemistry; D019204:GTP-Binding Proteins / Q000378:metabolism*; D015870:Gene Expression; D006801:Humans; D051379:Mice; D008840:Microfilament Proteins / Q000737:chemistry / Q000235:genetics / Q000378:metabolism*; D008969:Molecular Sequence Data; D051304:Profilins; D011506:Proteins / Q000737:chemistry; D029701:Saccharomyces cerevisiae Proteins; D014923:Wiskott-Aldrich Syndrome; D051316:Wiskott-Aldrich Syndrome Protein; D051300:Wiskott-Aldrich Syndrome Protein Family; D020744:rac GTP-Binding Proteins
D000199:Actins; D003285:Contractile Proteins; D005656:Fungal Proteins; D008840:Microfilament Proteins; C495738:PFN1 protein, human; C495739:Pfn1 protein, mouse; D051304:Profilins; D011506:Proteins; D029701:Saccharomyces cerevisiae Proteins; C090350:VRP1 protein, S cerevisiae; C495767:WAS protein, human; C495768:Was protein, mouse; C495774:Wasf1 protein, mouse; D051316:Wiskott-Aldrich Syndrome Protein; D051300:Wiskott-Aldrich Syndrome Protein Family; D019204:GTP-Binding Proteins; D020744:rac GTP-Binding Proteins