Compartmentalization of the exocyst complex in lipid rafts controls Glut4 vesicle tethering
Compartmentalization of the exocyst complex in lipid rafts controls Glut4 vesicle tethering
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DOI：
10.1091/mbc.e06-01-0030
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发表时间：
2006-05-01
影响因子：
3.3
通讯作者：
Saltiel, AR
中科院分区：
文献类型：
--
作者：
Inoue, M;Chiang, SH;Saltiel, AR
脂筏微域是信号转导的组织中心。我们在这里报道了由Exo70、Sec6和Sec8组成的胞外包囊复合体，它调节脂肪细胞中脂筏结构域中含有GLUT4的囊泡的区域化。Exo70被胰岛素激活后被G蛋白TC10招募，并伴随着Sec6和Sec8。这些蛋白质的敲除会阻止胰岛素刺激的葡萄糖摄取。此外，它们靶向脂筏是葡萄糖摄取和GLUT4在质膜上对接所必需的。这个复合体的组装也需要PDZ结构域蛋白SAP97，它是MAGUKs家族的成员，当它转移到脂筏上时，它会与Sec8结合。脂筏上的外囊组装为GLUT4囊泡建立了靶点，当胰岛素刺激细胞时，GLUT4囊泡瞬间与这些微域联系在一起。这些结果表明，TC10/外囊复合体/SAP97轴在脂肪细胞GLUT4囊泡与质膜的连接中起着重要作用。
Lipid raft microdomains act as organizing centers for signal transduction. We report here that the exocyst complex, consisting of Exo70, Sec6, and Sec8, regulates the compartmentalization of Glut4-containing vesicles at lipid raft domains in adipocytes. Exo70 is recruited by the G protein TC10 after activation by insulin and brings with it Sec6 and Sec8. Knockdowns of these proteins block insulin-stimulated glucose uptake. Moreover, their targeting to lipid rafts is required for glucose uptake and Glut4 docking at the plasma membrane. The assembly of this complex also requires the PDZ domain protein SAP97, a member of the MAGUKs family, which binds to Sec8 upon its translocation to the lipid raft. Exocyst assembly at lipid rafts sets up targeting sites for Glut4 vesicles, which transiently associate with these microdomains upon stimulation of cells with insulin. These results suggest that the TC10/exocyst complex/SAP97 axis plays an important role in the tethering of Glut4 vesicles to the plasma membrane in adipocytes.