MODULATION OF GDP DISSOCIATION INHIBITOR PROTEIN MEMBRANE RETENTION BY THE CELLULAR REDOX STATE IN ADIPOCYTES

Small GTPases of the Rab family play a key role in the regulation of v esicular transport in eukaryotic cells, As they cycle on and off membr anes, Rab proteins rely on the escort services of the GDP-dissociation inhibitor (GDI) proteins, While specific recognition of Rab-GDI compl exes by membrane targets is suggested, the mechanisms underlying the s ubsequent GDI release into the cytosol remain unknown. In this study, we demonstrate that modulations of the cellular redox status in intact rat fat cells, 3T3-L1 adipocytes in culture, and other cultured cell types result in rapid, effective, dose-dependent, and selective membra ne dynamics of GDI-1 and -2, membrane retention under reduced redox st ate, or dissociation under oxidized conditions. GDI retention on adipo cyte membranes is associated with a complete arrest of insulin-induced translocation of GLUT4 glucose transporters onto plasma membrane. Tog ether, these data suggest, first, that following Rab delivery to membr anes, GDI release is promoted by a shift in the redox state and, secon d, that arrest of GDIs on membranes inhibits intracellular membrane tr afficking events. (C) 1998 Academic Press.