Rab10, a target of the AS160 Rab GAP, is required for insulin-stimulated translocation of GLUT4 to the adipocyte plasma membrane.
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.
Sano
Hiroyuki
H
Department of Biochemistry, Dartmouth Medical School, Hanover, NH 03755, USA.
Eguez
Lorena
L
Teruel
Mary N
MN
Fukuda
Mitsunori
M
Chuang
Tuan D
TD
Chavez
Jose A
JA
Lienhard
Gustav E
GE
McGraw
Timothy E
TE
D041721:3T3-L1 Cells; D017667:Adipocytes / Q000378:metabolism* / Q000648:ultrastructure; D000818:Animals; D002462:Cell Membrane / Q000378:metabolism*; D005089:Exocytosis / Q000235:genetics; D020690:GTPase-Activating Proteins / Q000235:genetics / Q000502:physiology; D051275:Glucose Transporter Type 4 / Q000235:genetics / Q000378:metabolism*; D007328:Insulin / Q000494:pharmacology*; D051379:Mice; D030781:Organisms, Genetically Modified; D021381:Protein Transport / Q000187:drug effects; D011990:Receptors, Transferrin / Q000378:metabolism; D014162:Transfection; D020691:rab GTP-Binding Proteins / Q000235:genetics / Q000502:physiology*
D020690:GTPase-Activating Proteins; D051275:Glucose Transporter Type 4; D007328:Insulin; D011990:Receptors, Transferrin; C495693:Slc2a4 protein, mouse; C505647:Tbc1d4 protein, mouse; C520736:Rab10 protein, mouse; D020691:rab GTP-Binding Proteins