What is the primary function of Rab proteins in vesicle transport?
Rab small GTPases orchestrate specificity along endomembrane system as largest branch of Ras superfamily cycling between cytosol and membrane. GDP-bound Rabs kept soluble by guanine nucleotide dissociation inhibitor GDI that shields geranylgeranyl tails. Upon recruitment by specific guanine nucleotide exchange factors TRAPP, DENND, Mon1-Ccz1 at target organelles, they exchange GDP for GTP exposing N-terminal amphipathic helices and prenyl anchors firmly embedding in bilayer. GTP conformation exposes switch regions binding diverse effectors: long coiled-coil golgins like GM130, p115, tethering complexes CORVET, HOPS, Dsl1, GARP, TRAPPII, and motors kinesin, dynein, myosin Vb for movement along microtubules and actin. Effectors mediate vesicle capture at up to 200 nm bringing vesicles close for SNARE pairing. After fusion, TBC domain GAPs stimulate GTP hydrolysis returning Rab to GDP and GDI extraction for another cycle. Humans encode over 60 Rabs marking distinct compartments: Rab1 ER-Golgi, Rab5 early endosomes, Rab7 late, Rab11 recycling. They do not directly fuse membranes nor hydrolyze ATP nor degrade cargo.
Ref: Alberts et al., MBC, Chapter 13: Rab GTPases as vesicle tethering and targeting regulators.