RABAPTIN-5 IS A DIRECT EFFECTOR OF THE SMALL GTPASE RAB5 IN ENDOCYTICMEMBRANE-FUSION

We have identified a novel 100 kDa coiled-coil protein, rabaptin-5, th at specifically interacts with the GTP form of the small GTPase Rab5, a potent regulator of endocytic transport. It is mainly cytosolic, but a fraction colocalizes with Rab5 to early endosomes. Expression of a GTPase-deficient Rab5 mutant enhances the binding of rabaptin-5 to enl arged endosomes. Over-expression of rabaptin-5 alone is sufficient to promote expansion of early endosomes. Rab5 recruits rabaptin-5 to puri fied early endosomes in a GTP-dependent manner, demonstrating function al similarities with other members of the Ras superfamily. Immunodeple tion of rabaptin-5 from cytosol strongly inhibits Rab5-dependent early endosome fusion. Rabaptin-5 is thus a Rab effector required for membr ane docking and fusion.