Update on GLUT4 Vesicle Traffic: A Cornerstone of Insulin Action

Abstract

Glucose transport is rate limiting for dietary glucose utilization by muscle and fat. The glucose transporter GLUT4 is dynamically sorted and retained intracellularly and redistributes to the plasma membrane (PM) by insulin-regulated vesicular traffic, or 'GLUT4 translocation'. Here we emphasize recent findings in GLUT4 translocation research. The application of total internal reflection fluorescence microscopy (TIRFM) has increased our understanding of insulin-regulated events beneath the PM, such as vesicle tethering and membrane fusion. We describe recent findings on Akt-targeted Rab GTPase-activating proteins (GAPs) (TBC1D1, TBC1D4, TBC1D13) and downstream Rab GTPases (Rab8a, Rab10, Rab13, Rab14, and their effectors) along with the input of Rac1 and actin filaments, molecular motors [myosinVa (MyoVa), myosin1c (Myo1c), myosinIIA (MyoIIA)], and membrane fusion regulators (syntaxin4, munc18c, Doc2b). Collectively these findings reveal novel events in insulin-regulated GLUT4 traffic.

Keywords: GLUT4; Rab GTPases; actin cytoskeleton; insulin signaling; membrane fusion; vesicle traffic.