Caveolae internalization regulates integrin-dependent signaling pathways
Caveolae internalization regulates integrin-dependent signaling pathways
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DOI：
10.4161/cc.5.19.3264
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发表时间：
2006-10-01
期刊：
影响因子：
4.3
通讯作者：
Del Pozo, Miguel A.
中科院分区：
文献类型：
--
作者：
Echarri, Asier;Del Pozo, Miguel A.
整合素介导的粘附调节富含胆固醇的膜微域（CEMM）的运输。当细胞脱离细胞外基质（ECM）时，cemm经历快速内化并从质膜上清除。该途径调节整合素介导的Rac膜靶向，允许Rac与下游效应物偶联。cemm的内化是由动力蛋白-2（一种小泡动力学调节剂）和小泡蛋白-1（一种重要的小泡外壳蛋白）介导的。酪氨酸磷酸化的小窝蛋白-1在细胞脱离时从局灶黏附到小窝的易位诱导CEMM内化。值得注意的是，整合素介导的Erk、磷脂酰肌醇-3- oh激酶（PI3K）和Rac通路的调节依赖于caveolin-1。这些结果描述了一种新的途径，其中整合素通过抑制小窝蛋白-1依赖性内吞作用来防止Erk， PI3K和rac依赖性途径的下调。这一途径定义了一种新的分子机制，通过小洞蛋白-1调节细胞生长和抑制肿瘤。
Integrin-mediated adhesion regulates trafficking of cholesterol-enriched membrane microdomains (CEMM). Upon cell detachment from the extracellular matrix (ECM), CEMMs undergo rapid internalization and are cleared from the plasma membrane. This pathway regulates integrin-mediated Rac membrane targeting, allowing coupling of Rac to downstream effectors. Internalization of CEMMs is mediated by Dynamin-2, a regulator of caveolae dynamics, and caveolin-1, an essential caveolae coat protein. Translocation of tyrosine phosphorylated caveolin-1 from focal adhesions to caveolae upon cell detachment induces CEMM internalization. Notably, integrin-mediated regulation of Erk, phosphatidylinositol-3-OH kinase (PI3K) and Rac pathways is dependent on caveolin-1. These results describe a novel pathway in which integrins prevent downregulation of Erk, PI3K and Rac-dependent pathways by inhibiting caveolin-1-dependent endocytosis. This pathway define a novel molecular mechanism for regulated cell growth and tumor suppression by caveolin-1.