Sano Hiroyuki, Eguez Lorena, Teruel Mary N, Fukuda Mitsunori, Chuang Tuan D, Chavez Jose A, Lienhard Gustav E, McGraw Timothy E
Department of Biochemistry, Dartmouth Medical School, Hanover, NH 03755, USA.
Cell Metab. 2007 Apr;5(4):293-303. doi: 10.1016/j.cmet.2007.03.001.
GLUT4 trafficking to the plasma membrane of muscle and fat cells is regulated by insulin. An important component of insulin-regulated GLUT4 distribution is the Akt substrate AS160 rab GTPase-activating protein. Here we show that Rab10 functions as a downstream target of AS160 in the insulin-signaling pathway that regulates GLUT4 translocation in adipocytes. Overexpression of a mutant of Rab10 defective for GTP hydrolysis increased GLUT4 on the surface of basal adipocytes. Rab10 knockdown resulted in an attenuation of insulin-induced GLUT4 redistribution to the plasma membrane and a concomitant 2-fold decrease in GLUT4 exocytosis rate. Re-expression of a wild-type Rab10 restored normal GLUT4 translocation. The basal increase in plasma-membrane GLUT4 due to AS160 knockdown was partially blocked by knocking down Rab10 in the same cells, further indicating that Rab10 is a target of AS160 and a positive regulator of GLUT4 trafficking to the cell surface upon insulin stimulation.
葡萄糖转运蛋白4（GLUT4）向肌肉和脂肪细胞质膜的转运受胰岛素调节。胰岛素调节的GLUT4分布的一个重要组成部分是Akt底物AS160（一种rab GTP酶激活蛋白）。在此我们表明，在调节脂肪细胞中GLUT4转运的胰岛素信号通路中，Rab10作为AS160的下游靶点发挥作用。对GTP水解有缺陷的Rab10突变体的过表达增加了基础脂肪细胞表面的GLUT4。Rab10基因敲低导致胰岛素诱导的GLUT4向质膜的重新分布减弱，同时GLUT4胞吐率降低2倍。野生型Rab10的重新表达恢复了正常的GLUT4转运。在同一细胞中敲低Rab10可部分阻断因AS160基因敲低导致的质膜GLUT4的基础增加，这进一步表明Rab10是AS160的靶点，并且是胰岛素刺激后GLUT4向细胞表面转运的正向调节因子。
