RESUMEN
Small GTPases of the Rab family play a key role in the regulation of vesicular transport in eukaryotic cells. As they cycle on and off membranes, Rab proteins rely on the escort services of the GDP-dissociation inhibitor (GDI) proteins. While specific recognition of Rab-GDI complexes by membrane targets is suggested, the mechanisms underlying the subsequent 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 membrane dynamics of GDI-1 and -2, membrane retention under reduced redox state, or dissociation under oxidized conditions. GDI retention on adipocyte membranes is associated with a complete arrest of insulin-induced translocation of GLUT4 glucose transporters onto plasma membrane. Together, these data suggest, first, that following Rab delivery to membranes, GDI release is promoted by a shift in the redox state and, second, that arrest of GDIs on membranes inhibits intracellular membrane trafficking events.
