Arf6 and microtubules in adhesion-dependent trafficking of lipid rafts
Arf6 and microtubules in adhesion-dependent trafficking of lipid rafts
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DOI：
10.1038/ncb1657
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发表时间：
2007-12-01
影响因子：
21.3
通讯作者：
Schwartz, Martin Alexander
中科院分区：
文献类型：
--
作者：
Balasubramanian, Nagaraj;Scott, David W.;Schwartz, Martin Alexander
整合素介导的黏附调节脂筏内rac1的膜结合位点。细胞从底物上分离，通过小窝蛋白依赖的内化，触发木筏从质膜上的清除。小的GTP酶Arf6和微管也调节依赖RAC的细胞的扩散和迁移，但其机制尚不清楚。在这里，我们展示了木筏脱离后的内吞作用需要F-肌动蛋白，随后微管依赖于运输到再循环的内小体。当细胞在纤维连接蛋白上复制时，木筏以Arf6依赖的方式退出回收内小体，并沿着微管返回质膜。这两个步骤都是质膜靶向rac1及其激活所必需的。因此，这些数据定义了一条新的膜筏运输途径，该途径对锚定依赖的信号转导至关重要。
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.