del Pozo Miguel A, Alderson Nazilla B, Kiosses William B, Chiang Hui-Hsien, Anderson Richard G W, Schwartz Martin A
Department of Cell Biology, Scripps Research Institute, 10550 North Torrey Pines Road, La Jolla, CA 92037, USA.
Science. 2004 Feb 6;303(5659):839-42. doi: 10.1126/science.1092571.
Translocation of the small GTP-binding protein Rac1 to the cell plasma membrane is essential for activating downstream effectors and requires integrin-mediated adhesion of cells to extracellular matrix. We report that active Rac1 binds preferentially to low-density, cholesterol-rich membranes, and specificity is determined at least in part by membrane lipids. Cell detachment triggered internalization of plasma membrane cholesterol and lipid raft markers. Preventing internalization maintained Rac1 membrane targeting and effector activation in nonadherent cells. Regulation of lipid rafts by integrin signals may regulate the location of membrane domains such as lipid rafts and thereby control domain-specific signaling events in anchorage-dependent cells.
小GTP结合蛋白Rac1易位至细胞质膜对于激活下游效应器至关重要，并且需要整合素介导细胞与细胞外基质的黏附。我们报告称，活性Rac1优先结合低密度、富含胆固醇的膜，其特异性至少部分由膜脂决定。细胞脱离触发了质膜胆固醇和脂筏标志物的内化。阻止内化可维持非黏附细胞中Rac1的膜靶向作用和效应器激活。整合素信号对脂筏的调节可能会调控脂筏等膜结构域的位置，从而控制锚定依赖性细胞中的结构域特异性信号事件。
