Small G proteins in insulin action: Rab and Rho families at the crossroads of signal transduction and GLUT4 vesicle traffic.
Insulin stimulates glucose uptake into muscle and adipose tissues through glucose transporter 4 (GLUT4). GLUT4 cycles between the intracellular compartments and the plasma membrane. GLUT4 traffic-regulating insulin signals are largely within the insulin receptor-insulin receptor substrate-phosphatidylinositol 3-kinase (IR-IRS-PI3K) axis. In muscle cells, insulin signal bifurcates downstream of the PI3K into one arm leading to the activation of the Ser/Thr kinases Akt and atypical protein kinase C, and another leading to the activation of Rho family protein Rac1 leading to actin remodelling. Activated Akt inactivates AS160, a GTPase-activating protein for Rab family small G proteins. Here we review the roles of Rab and Rho proteins, particularly Rab substrates of AS160 and Rac1, in insulin-stimulated GLUT4 traffic. We discuss: (1) how distinct steps in GLUT4 traffic may be regulated by discrete Rab proteins, and (2) the importance of Rac1 activation in insulin-induced actin remodelling in muscle cells, a key element for the net gain in surface GLUT4.
Ishikura
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Program in Cell Biology, The Hospital for Sick Children, Toronto, ON, Canada.
Koshkina
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Klip
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D000199:Actins / Q000378:metabolism; D000818:Animals; D051275:Glucose Transporter Type 4 / Q000378:metabolism*; D006801:Humans; D007328:Insulin / Q000502:physiology*; D020559:Monomeric GTP-Binding Proteins / Q000502:physiology*; D018482:Muscle, Skeletal / Q000378:metabolism; D021381:Protein Transport / Q000502:physiology; D015398:Signal Transduction / Q000502:physiology; D014178:Translocation, Genetic / Q000502:physiology; D020691:rab GTP-Binding Proteins / Q000502:physiology*; D020744:rac GTP-Binding Proteins / Q000502:physiology*
D000199:Actins; D051275:Glucose Transporter Type 4; D007328:Insulin; D020559:Monomeric GTP-Binding Proteins; D020691:rab GTP-Binding Proteins; D020744:rac GTP-Binding Proteins