The atypical Rho family GTPase Wrch-1 regulates focal adhesion formation and cell migration
The atypical Rho family GTPase Wrch-1 regulates focal adhesion formation and cell migration
复制标题
DOI：
10.1242/jcs.03456
复制
发表时间：
2007-06-01
影响因子：
4
通讯作者：
Symons, Marc
中科院分区：
文献类型：
--
作者：
Chuang, Ya-Yu;Valster, Aline;Symons, Marc
Wnt调控的Cdc 42同源基因是Rho家族的一个新成员，被鉴定为Wnt-1转录上调的基因。Gtch-1没有可检测到的GTP酶活性，并显示出非常高的内在鸟嘌呤核苷酸交换，这意味着它是组成型GTP结合的。其生物学功能在很大程度上仍有待研究。在这里，我们报告，PDCH-1显着定位于局灶性粘连。通过小干扰RNA消耗PDCH-1增加粘着斑的形成，而PDCH-1过表达分解粘着斑。PDCH-1耗竭抑制肌球蛋白轻链磷酸化，这反过来导致局灶性粘连数量增加，并抑制响应伤口愈合的细胞迁移。Escherich-I的耗尽也抑制Akt和JNK活化。虽然Akt和JNK的药理学抑制剂抑制细胞迁移，但它们不影响粘着斑。因此，我们的数据表明，PDCH-1通过多种机制调节细胞迁移：一方面，PDCH-1通过调节肌球蛋白轻链控制局灶性粘连，另一方面，PDCH-1刺激Akt和JNK的激活。
Wrch-1 (Wnt-regulated Cdc42 homolog) is a new member of the Rho family that was identified as a gene transcriptionally upregulated by Wnt-1. Wrch-1 has no detectable GTPase activity and displays very high intrinsic guanine nucleotide exchange, implying that it is constitutively GTP-bound. The biological functions of Wrch-1 largely remain to be characterized. Here, we report that Wrch-1 prominently localizes to focal adhesions. Depletion of Wrch-1 by small interfering RNA increases focal adhesion formation, whereas Wrch-1 overexpression disassembles focal adhesions. Wrch-1 depletion inhibits myosin-light-chain phosphorylation, which in turn leads to an increase in the number of focal adhesions and inhibits cell migration in response to wound healing. Depletion of Wrch-1 also inhibits Akt and JNK activation. Although pharmacological inhibitors of Akt and JNK inhibit cell migration, they do not affect focal adhesions. Thus, our data suggest that Wrch-1 regulates cell migration by multiple mechanisms: on the one hand Wrch-1 controls focal adhesions by regulating myosin light chain and on the other hand Wrch-1 stimulates the activation of Akt and JNK.