Description
The Rab family of GTP-binding proteins are members of the Ras superfamily of small G proteins, and participate in multiple steps of the membrane trafficking. Rab3A participates in the fusion of synaptic vesicles during neurotransmitter release, a process regulated by GDP/GDP exchange cofactors such as GAP, GDI, GRF, and rabphilin. Rab4 regulates recycling of proteins from the early endosome to the surface of many cell types, regulating glucose transporter and transferrin receptor cell surface localization. Rab5 regulates the fusion of plasma membrane-derived clathrin-coated vesicles with early endosomes and homotypic fusion among early endosomes.Rab5 is a 24kD GTP-binding protein that regulates the fusion of plasma membrane-derived clathrin-coated vesicles with early endosomes and homotypic fusion among early endosomes. It is localized to the cytoplasmic side of the plasma membrane, clathrin-coated vesicles, and early endosomes. Rab5 is believed to regulate vesicle fusion through a cycle of GDP/GTP exchange and GTP hydrolysis. The different guanine nucleotide binding states of Rab5 is postulated to affect its ability to associate or dissociate with membranes during endocytotic membrane traffic. Its GTP-bound form, which represents the active form of Rab5, associates with membrane and regulates vesicle docking and fusion. Studies using Rab5 mutant that hydrolysed xanthosine 5í-triphosphate (XTP) indicated that nucleotide hydrolysis occurs even in the absence of membrane fusion. GTP hydrolysis by Rab5 is postulated to determine the frequency of membrane docking and fusion events