RAB GDP DISSOCIATION INHIBITOR AS A GENERAL REGULATOR FOR THE MEMBRANE ASSOCIATION OF RAB PROTEINS

Rab proteins comprise a family of small GTPases that serve a regulator y role in membrane traffic. These proteins are in part cytosolic and i n part associated with the membranes of specific exocytic and endocyti c organelles. Smg p25A/rab3A GDI, a cytosolic protein which inhibits t he dissociation of GDP from smg p25A/rab3A, Sec4p, and rab11, has also been found to prevent association of rab3A with the membrane. In this study, we have used Madin-Darby canine kidney cells permeabilized wit h the bacterial toxin streptolysin O to test the general activity of r ab3A GDI in modulating the membrane association of various small GTP-b inding proteins. Rab3A GDP dissociation inhibitor (GDI) removed from t he membrane all rab proteins we have tested and inhibited the membrane binding of in vitro translated rab proteins. However, rab3A GDI had a limited effect on the membrane association of a mutant rab5 protein w hich contained a farnesylated cysteine motif. Finally, we found that, although rab3A GDI resides primarily in the cytosol, it is also associ ated with compartments of the exocytic and endocytic pathways. Since r ab3A GDI can modulate the membrane association of various rab proteins , we propose to rename it rab GDI.