Gd. Holman et al., INSULIN-STIMULATED GLUT4 GLUCOSE-TRANSPORTER RECYCLING - A PROBLEM INMEMBRANE-PROTEIN SUBCELLULAR TRAFFICKING THROUGH MULTIPLE POOLS, The Journal of biological chemistry, 269(26), 1994, pp. 17516-17524
The subcellular trafficking of GLUT4 in isolated rat adipose cells and
3T3-L1 adipocytes exhibits many of the properties observed in regulat
ed secretory processes and neurosecretion. GLUT4 is sorted and sequest
ered from endosomes into a specialized secretory compartment in the ba
sal state and the initial stimulation of its exocytosis by insulin is
more rapid than its recycling through the endosomes and secretory comp
artment during the steady-state response to insulin. We present a math
ematical analysis which shows that this behavior is inconsistent with
a simple 2-pool model with one plasma membrane and one intracellular c
ompartment, but that a 3-pool model, with two intracellular compartmen
ts, can simulate these properties. We extend this model to include the
presence of occluded pools in the plasma membrane. Our analysis compa
res the behavior expected when these occluded pools are precursors in
stimulation and/or clathrin-associated-like intermediates in endocytos
is. The presence of a precursor occluded pool can account for a lag be
tween the appearance of GLUT4 in the membrane and before the full stim
ulation of glucose transport activity. The analysis also shows that si
nce the pool size of the occluded GLUT4 is relatively small, the forma
tion of endocytic occluded intermediates such as GLUT4 in clathrin-coa
ted pits is likely to be slow compared with the rate of endocytosis of
the coated vesicles.