The Rab proteins are small GTP-binding molecules. They are localized to specific intracellular vesicles and organelles and are important for vesicular trafficking, cycling between an active GTP-bound and inactive GDP-bound form. Rab5 is associated with vesicle trafficking between the early endosomes and plasma membrane. In vitro, Rab5 proteins are removed from membranes by a GDP dissociation inhibitor protein (rabGDI). This leads to the formation of a cytosolic Rab5-rabGDI complex. Rab5 may insert into membranes by a multistep process in which a transient GDP-Rab5 intermediate is formed and converted into GTP- Rab5. Rabaptin-5 interacts with GTP-Rab5, and is recruited to the endosomal fraction in a Rab5/GTP-dependent manner. Removal of Rabaptin-5 from the cytosol substantially impairs GTP and Rab5-dependent endosomal fusion. Rabex-5 forms a complex with Rabaptin-5 and displays GDP/GTP exchange activity on Rab5 that promotes interaction between Rabaptin-5 and Rab5. Rabex-5 is also known as Rin2 based on its 15% identitiy with the RasGTPase-binding protein Rin1. Thus, Rabex-5/Rabaptin-5 complex is critical for Rab5 GDP/GTP exchange and membrane-associated activity.
