Figure 9.

A model of the intracellular GLUT4 compartment and insulin-stimulated GLUT4 traffic in L6 muscle cells. Under basal conditions, GLUT4 is continuously recycled to and from the plasma membrane (PM) but is largely sequestered intracellularly within the endosomal sorting system (SE) and a specialized GLUT4 vesicular (SV) pool. Other proteins, such as the transferrin receptor (TfR), recycle constitutively through the recycling endosome (RE). The mobilization of specific proteins out of both the RE and SV compartments can be modulated by insulin, possibly by differential protein sorting out of the SE. Insulin potentiates the exocytosis of GLUT4 from the SV pool by inducing the Rac-mediated formation of cortical actin mesh structures beneath the cell surface. This remodeled actin mesh recruits GLUT4-containing vesicles from the SV, allowing them to fuse with the PM. These insulin-responsive GLUT4 vesicles found in the actin mesh also comprise VAMP2, a vesicle SNARE that is essential for the incorporation of GLUT4 into the plasma membrane.