Echarri Asier, Del Pozo Miguel A
Integrin Signaling Laboratory, Centro Nacional de Investigaciones Cardiovasculares, Madrid, Spain.
Cell Cycle. 2006 Oct;5(19):2179-82. doi: 10.4161/cc.5.19.3264. Epub 2006 Oct 1.
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.
整合素介导的黏附作用调节富含胆固醇的膜微区（CEMM）的运输。当细胞与细胞外基质（ECM）脱离时，CEMM会迅速内化并从质膜上清除。该途径调节整合素介导的Rac膜靶向作用，使Rac与下游效应器偶联。CEMM的内化由发动蛋白2（一种小窝动力学调节剂）和小窝蛋白1（一种必不可少的小窝衣被蛋白）介导。细胞脱离时，酪氨酸磷酸化的小窝蛋白1从黏着斑转位至小窝会诱导CEMM内化。值得注意的是，整合素介导的细胞外信号调节激酶（Erk）、磷脂酰肌醇-3-羟基激酶（PI3K）和Rac信号通路的调节依赖于小窝蛋白1。这些结果描述了一种新途径，即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依赖性信号通路的下调。该途径为小窝蛋白1调节细胞生长和肿瘤抑制作用定义了一种新的分子机制。
