Functional characterization of vesicle-snares in GLUT4 glucose transporter vesicle traffic.

摘要

Muscle maintains peripheral glucose homeostasis by increasing glucose uptake through GLUT4 glucose transporters recruited to the cell surface by insulin. A defect in insulin action leading to the plasma membrane incorporation of GLUT4 may result in impaired glucose transport. Insulin resistance of GLUT4 movement and glucose utilization in muscle is evident within patients presenting type 2 and obesity-dependent diabetes; underscoring the need to understand GLUT4 traffic in muscle.; GLUT4 exists within several intracellular compartments, recycles constitutively and translocates in response to other stimuli. In this thesis, we explored the role of vesicle-SNARE proteins in traffic from GLUT4 donor pools by using mutant VAMP proteins to recover tetanus toxin-inhibited GLUT4 traffic. Toxin-resistant VAMP2, not VAMP3, rescued toxin-inhibited insulin-mediated GLUT4 traffic. Also, VAMP2 accumulated distinctly in the insulin-remodelled actin mesh. Thus, we conclude that VAMP2 functions as a selective fusogen for insulin-responsive GLUT4 traffic from a specialized vesicular pool requiring actin remodelling.