Caveolin-1 regulates cell polarization and directional migration through Src kinase and Rho GTPases.
Caveolin-1 regulates cell polarization and directional migration through Src kinase and Rho GTPases.
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Caveolin-1通过SRC激酶和Rho GTPases调节细胞极化和定向迁移。
DOI：
10.1083/jcb.200701006
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发表时间：
2007-05-21
期刊：
影响因子：
--
通讯作者：
del Pozo MA
中科院分区：
文献类型：
--
作者：
Grande-García A;Echarri A;de Rooij J;Alderson NB;Waterman-Storer CM;Valdivielso JM;del Pozo MA
发育、血管生成、伤口愈合和转移都涉及细胞响应细胞外环境变化的运动。为了确定小窝蛋白-1是否在细胞迁移中起作用，我们使用了基因敲除小鼠的成纤维细胞。小窝蛋白-1缺陷细胞失去正常的细胞极性，表现出受损的伤口愈合，并具有降低的Rho和增加的Rac和Cdc 42 GTdR活性。迁移的方向性持续性丧失，细胞对外部方向性刺激的反应受损。Src失活和p190 RhoGAP敲低均恢复了小窝蛋白-1缺陷细胞的野生型表型，表明小窝蛋白-1通过Src-p190 RhoGAP通路的失活刺激正常的Rho GTP负载。这些发现强调了小窝蛋白-1在定向迁移过程中通过协调Src激酶和Rho GTPases的信号传导建立细胞极性的重要性。
Development, angiogenesis, wound healing, and metastasis all involve the movement of cells in response to changes in the extracellular environment. To determine whether caveolin-1 plays a role in cell migration, we have used fibroblasts from knockout mice. Caveolin-1–deficient cells lose normal cell polarity, exhibit impaired wound healing, and have decreased Rho and increased Rac and Cdc42 GTPase activities. Directional persistency of migration is lost, and the cells show an impaired response to external directional stimuli. Both Src inactivation and p190RhoGAP knockdown restore the wild-type phenotype to caveolin-1–deficient cells, suggesting that caveolin-1 stimulates normal Rho GTP loading through inactivation of the Src–p190RhoGAP pathway. These findings highlight the importance of caveolin-1 in the establishment of cell polarity during directional migration through coordination of the signaling of Src kinase and Rho GTPases.