MEMBRANE TARGETING OF THE SMALL GTPASE RAB9 IS ACCOMPANIED BY NUCLEOTIDE EXCHANGE

THE Rab GTPases are key regulators of vesicular transport(1-6). A frac tion of Rab proteins is present in the cytosol, bound with GDP, comple xed tb a protein termed GDI(7-10). Rab9 is localized primarily to late endosomes, where it aids the transport of mannose 6-phosphate recepto rs to the trans-Golgi network(11). It has been proposed that Rab prote ins are delivered to specific membranes by GDI, and that this process is accompanied by the exchange of bound GDP for GTP(1-3). In addition, Rab localization requires carboxy-terminal prenylation and specific s tructural determinants(12-14). Here we describe the reconstitution of the selective targeting of prenylated Rab9 protein onto late endosome membranes and show that this process is accompanied by endosome-trigge red nucleotide exchange.