Activation of Rac1 by RhoG regulates cell migration
Activation of Rac1 by RhoG regulates cell migration
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DOI：
10.1242/jcs.02720
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发表时间：
2006-01-01
影响因子：
4
通讯作者：
Negishi, M
中科院分区：
文献类型：
--
作者：
Katoh, H;Hiramoto, K;Negishi, M
细胞迁移对于正常发育和许多病理过程是必不可少的。Rho家族小GTPases在这一事件中发挥着重要作用。特别是，Rac调节迁移过程中前缘的片状伪足形成。小GTdR RhoG通过其效应子埃尔莫和ELMO结合蛋白Dock180激活Rac，Dock180作为Rac特异性鸟嘌呤核苷酸交换因子发挥作用。在这里，我们研究了RhoG在细胞迁移中的作用。RNA干扰介导的RhoG在HeLa细胞中的敲低减少了Transwell和划痕迁移试验中的细胞迁移。在RhoG基因敲低的细胞中，Rac1的激活和在前缘响应于创伤的片状伪足的形成被减弱。相比之下，活性RhoG的表达通过埃尔莫和Dock180促进细胞迁移。然而，Dock180与Crk的相互作用对于RhoG激活Rac1和促进细胞迁移是无效的。总之，这些结果表明，RhoG有助于调节迁移细胞中的Rac活性。
Cell migration is essential for normal development and many pathological processes. Rho-family small GTPases play important roles in this event. In particular, Rac regulates lamellipodia formation at the leading edge during migration. The small GTPase RhoG activates Rac through its effector ELMO and the ELMO-binding protein Dock180, which functions as a Rac-specific guanine nucleotide exchange factor. Here we investigated the role of RhoG in cell migration. RNA interference-mediated knockdown of RhoG in HeLa cells reduced cell migration in Transwell and scratch-wound migration assays. In RhoG-knockdown cells, activation of Rac1 and formation of lamellipodia at the leading edge in response to wounding were attenuated. By contrast, expression of active RhoG promoted cell migration through ELMO and Dock180. However, the interaction of Dock180 with Crk was dispensable for the activation of Rac1 and promotion of cell migration by RhoG. Taken together, these results suggest that RhoG contributes to the regulation of Rac activity in migrating cells.