Oligomerization of rab/effector complexes in the regulation of vesicle trafficking

Rabs comprise the largest member of the Ras superfamily of small GTPases with over 60 proteins in mammals and 11 proteins in yeast. Like all small GTPases, Rabs oscillate between an inactive GDP-bound conformation and an active GTP-bound state that is tethered to lipid membranes via a C-terminal prenylation site on conserved cysteine residues. In their active state, Rabs regulate various aspects of membrane trafficking, including vesicle formation, transport, docking, and fusion. The critical element of biological activity is the recruitment of cytosolic effector proteins to specific endomembranes by active Rabs. The importance of Rabs in cellular processes is apparent from their links to genetic disorders, immunodeficiency, cancer, and pathogen invasion. During the last decade, numerous structures of complexes have shed light on the molecular basis for Rab/effector specificity and their topological organization on subcellular membranes. Here, I review the known structures of Rab/effector complexes and their modes of oligomerization. This is followed by a brief discussion on the thermodynamics of effector recruitment, which has not been documented sufficiently in previous reviews. A summary of diseases associated with Rab/effector trafficking pathways concludes this chapter.