Balasubramanian Nagaraj, Scott David W, Castle J David, Casanova James E, Schwartz Martin Alexander
Robert M. Beirne Cardiovascular Research Center, Mellon Prostate Cancer Research Institute, University of Virginia, Charlottesville, Virginia 22908, USA.
Nat Cell Biol. 2007 Dec;9(12):1381-91. doi: 10.1038/ncb1657. Epub 2007 Nov 18.
Integrin-mediated adhesion regulates membrane binding sites for Rac1 within lipid rafts. Detachment of cells from the substratum triggers the clearance of rafts from the plasma membrane through caveolin-dependent internalization. The small GTPase Arf6 and microtubules also regulate Rac-dependent cell spreading and migration, but the mechanisms are poorly understood. Here we show that endocytosis of rafts after detachment requires F-actin, followed by microtubule-dependent trafficking to recycling endosomes. When cells are replated on fibronectin, rafts exit from recycling endosomes in an Arf6-dependent manner and return to the plasma membrane along microtubules. Both of these steps are required for the plasma membrane targeting of Rac1 and for its activation. These data therefore define a new membrane raft trafficking pathway that is crucial for anchorage-dependent signalling.
整合素介导的黏附作用调节脂筏内Rac1的膜结合位点。细胞与基质脱离会通过小窝蛋白依赖的内吞作用引发脂筏从质膜上清除。小GTP酶Arf6和微管也调节Rac依赖的细胞铺展和迁移，但其机制尚不清楚。我们在此表明，脱离后脂筏的内吞作用需要F-肌动蛋白，随后通过微管依赖的运输至回收内体。当细胞重新接种到纤连蛋白上时，脂筏以Arf6依赖的方式从回收内体中出来，并沿微管返回质膜。这两个步骤对于Rac1靶向质膜及其激活都是必需的。因此，这些数据定义了一条新的膜脂筏运输途径，该途径对于锚定依赖信号传导至关重要。
