Heterotetramer formation of prenylated Rab3A with two Rabphilin-3A molecules.

Rab3A small GTP-binding protein and its putative target protein, named Rabphilin-3A, are implicated in neurotransmitter release. We have investigated here the function of the lipid modifications of Rab3A (Mr approximately 25,000) in its interaction with Rabphilin-3A (Mr approximately 80,000). Lipid-modified GTP-Rab3A dimerized and lipid-unmodified one monomerized. Lipid-modified GTP-Rab3A (Mr approximately 50,000) formed a heterotetramer (Mr approximately 210,000) with two Rabphilin-3A molecules, whereas lipid-unmodified GTP-Rab3A formed a heterodimer (Mr approximately 105,000) with one Rabphilin-3A molecule. These results indicate that two lipid-modified GTP-Rab3A molecules form a heterotetramer with two Rabphilin-3A molecules.