Rab GTPases as coordinators of vesicle traffic

Abstract

Rab GTPases control all aspects of intracellular vesicle trafficking by acting as regulatable switches that recruit effector molecules when in their active GTP-bound form. There are approximately 60 different Rab GTPases in humans that are associated with distinct intracellular membranes. Rab GTPases are turned on and off by specific guanine nucleotide exchange factors (GEFs) and GTPase-activating proteins (GAPs), respectively. Rab effectors come in many forms and range from vesicle tethers to motors, kinases, phosphatases and various adaptor proteins. Different Rab GTPases are restricted to distinct subdomains of the same organelle membrane and can crosstalk through effectors that are coupled to GEFs or GAPs. Rab GTPases are essential for physiological processes such as immunity, hormone secretion and neurotransmission, and their genetic inactivation is associated with diseases.