Rab5a: Proteins and Enzymes

Rab5 is a 24 kDa GTP-binding protein that regulates the fusion of plasma membrane -derived clathrin-coated vesicles with early endosomes , and homotypic fusion among early endosomes1. Localized to the cytoplasmic side of the plasma membrane, clathrin -coated vesicles and early endosomes, Rab5 appears to regulate vesicle fusion through a cycle of GDP/GTP e xchange and GTP hydrolysis. The different guanine nuc leotide binding states of Rab5 may affect its ability to associate or dissociate with membranes during endocytotic membrane traffic. The GTP-bound, or active, form of Rab5 associates with membrane s and regulates vesicle docking and fusion. Studies using a Rab5 mutant that hydrolyzed xanthosine 5 -triphosphate (XTP) indicated that nucleotide hydrolysis occurs even in the absence of membrane fusion. GTP hydrolysis by Rab5 may determine the frequency of membrane docking and fusion events.