Rab3GAP

Rab3GAP refers to the Rab3 GTPase-activating protein complex that regulates Rab3 family small GTPases involved in synaptic vesicle trafficking. It forms a heterodimer consisting of Rab3GAP1 and Rab3GAP2. The Rab3GAP1 subunit provides the catalytic GTPase-activating function, while Rab3GAP2 acts as a regulatory subunit required for full activity and proper localization of the complex.

The primary role of Rab3GAP is to stimulate GTP hydrolysis on Rab3 proteins (Rab3A-D), converting them from the active GTP-bound state to the inactive GDP-bound state. This inactivation is part of the Rab3 GTPase cycle that modulates vesicle docking, priming, and the timing of neurotransmitter release at presynaptic terminals. The Rab3GAP complex localizes to synaptic vesicles and related membranes, and its activity helps coordinate vesicle cycling with exocytosis.

Genetic mutations affecting Rab3GAP1, and less commonly Rab3GAP2, are associated with Warburg micro syndrome, a rare autosomal recessive developmental disorder. The condition is characterized by severe ocular abnormalities (such as cataracts and microphthalmia), brain malformations, microcephaly, and growth retardation. The syndrome highlights the importance of Rab3GAP-mediated Rab3 regulation for neural development and synaptic function.

See also: Rab family GTPases, GTPase-activating proteins, Warburg micro syndrome.