RAB 3D IN RAT ADIPOSE-CELLS AND ITS OVEREXPRESSION IN GENETIC OBESITY(ZUCKER FATTY RAT)

Members of the Rab 3 subfamily of low-molecular-mass GTP-binding prote ins have been functionally implicated in regulated exocytosis. The aim of the present study was to examine the subcellular distribution of a member of this family, Rab 3D, in rat adipose cells, given the hypoth esis that this protein might be involved in insulin-stimulated GLUT4 e xocytosis. We show that Rab 3D immunoreactivity is associated predomin antly with the high-density microsomal fraction, where the signal inte nsity is 3- and 7-fold greater than that in plasma membranes and low-d ensity microsomes respectively. Rab 3D does not co-localize with GLUT4 on immune-isolated intracellular vesicles and, unlike GLUT4, it is no t redistributed in response to insulin. Thus, if Rab 3D plays a role i n GLUT4 trafficking, it relies on mechanisms independent of relocation . We observed that Rab 3D is overexpressed in adipose cells of obese ( fa/fa) Zucker rats, in a tissue- and isoform-specific manner. The path ophysiological significance of this defect remains elusive. This could form the molecular basis for altered adipose secretory function in ob esity.