WAVE, a novel WASP-family protein involved in actin reorganization induced by Rac
WAVE, a novel WASP-family protein involved in actin reorganization induced by Rac
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DOI：
10.1093/emboj/17.23.6932
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发表时间：
1998-12-01
期刊：
影响因子：
11.4
通讯作者：
Takenawa, T
中科院分区：
文献类型：
--
作者：
Miki, H;Suetsugu, S;Takenawa, T
Rac 是一种 Rho 家族小 GTP 酶，可诱导膜褶皱的形成。然而，人们对Pac诱导的肌动蛋白细胞骨架重组（皱褶形成所必需的）是如何调节的知之甚少。在这里，我们鉴定了一种新的Wiskott-Aldrich综合征蛋白（WASP）家族蛋白，WASP家族Verprolin同源蛋白（WAVE），作为Rac下游肌动蛋白重组的调节剂，异位表达的WAVE诱导与表达的WAVE本身重叠的肌动蛋白丝簇的形成。在这种肌动蛋白聚类中，Profilin（一种单体肌动蛋白结合蛋白，被认为参与肌动蛋白聚合）被证明是必不可少的。显性活性 Pac 突变体的表达诱导内源性 WAVE 从细胞质易位到膜皱褶区域。此外，不能诱导肌动蛋白重组的 Delta VPH WAVE 突变体的共表达特异性抑制 Pac 诱导的皱褶形成，但对 Cdc42 诱导的肌动蛋白微刺形成没有影响，这种现象也依赖于快速肌动蛋白重组。 Delta VPH WAVE 还可以抑制瑞士 3T3 细胞中血小板衍生生长因子诱导的膜褶皱形成。综上所述，我们得出结论，WAVE 在 Pac 下游调节膜褶皱所需的肌动蛋白细胞骨架方面发挥着关键作用。
Rac is a Rho-family small GTPase that induces the formation of membrane ruffles. However, it is poorly understood how Pac-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 Pac mutant induces the translocation of endogenous WAVE from the cytosol to membrane ruffling areas, Furthermore, the co-expression of a Delta VPH WAVE mutant that cannot induce actin reorganization specifically suppresses the ruffle formation induced by Pac, but has no effect on Cdc42-induced actin-microspike formation, a phenomenon that is also known to be dependent on rapid actin reorganization. The Delta VPH 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 Pac in regulating the actin cytoskeleton required for membrane ruffling.