GLUT4 - At the cross roads between membrane trafficking and signal transduction

GLUT4 is a mammalian facilitative glucose transporter that is highly expres sed in adipose tissue and striated muscle. In response to insulin, GLUT4 mo ves from intracellular storage areas to the plasma membrane, thus increasin g cellular glucose uptake. While the verification of this 'translocation hy pothesis' (Cushman SW. Wardzala LJ. J Biol Chem 1980;255: 4758-4762 and Suz uki K, Kono T. Proc Natl Acad Sci 1980;77: 2542-2545) has increased our und erstanding of insulin-regulated glucose transport, a number of fundamental questions remain unanswered. Where is GLUT4 stored within the basal cell? H ow does GLUT4 move to the cell surface and what mechanism does insulin empl oy to accelerate this process) Ultimately we require a convergence of traff icking studies with research in signal transduction. However, despite more than 30 years of intensive research we have still not reached this point. T he problem is complex, involving at least two separate signal transduction pathways which feed into what appears to be a very dynamic sorting process. Below we discuss some of these complexities and highlight new data that ar e bringing us closer to the resolution of these questions.