Grande-García Araceli, Echarri Asier, de Rooij Johan, Alderson Nazilla B, Waterman-Storer Clare M, Valdivielso José M, del Pozo Miguel A
Integrin Signaling Laboratory, Department of Vascular Biology and Inflammation, Centro Nacional de Investigaciones Cardiovasculares, Madrid, Spain.
J Cell Biol. 2007 May 21;177(4):683-94. doi: 10.1083/jcb.200701006.
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.
发育、血管生成、伤口愈合和转移均涉及细胞响应细胞外环境变化而发生的移动。为了确定小窝蛋白-1是否在细胞迁移中发挥作用，我们使用了基因敲除小鼠的成纤维细胞。缺乏小窝蛋白-1的细胞失去正常的细胞极性，伤口愈合受损，Rho活性降低，Rac和Cdc42 GTP酶活性增加。迁移的定向持续性丧失，细胞对外界定向刺激的反应受损。Src失活和p190RhoGAP敲低均可使小窝蛋白-1缺陷细胞恢复野生型表型，这表明小窝蛋白-1通过Src-p190RhoGAP途径的失活刺激正常的Rho GTP负载。这些发现突出了小窝蛋白-1在通过协调Src激酶和Rho GTP酶的信号传导进行定向迁移过程中建立细胞极性的重要性。
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