Rab3mediated

Rab3-mediated refers to cellular processes governed by the Rab3 subfamily of small GTPases, which regulate regulated exocytosis and vesicle trafficking in neurons and secretory cells. The Rab3 family includes Rab3A, Rab3B, Rab3C, and Rab3D. These proteins localize primarily to secretory vesicles and cycle between an inactive GDP-bound state and an active GTP-bound state. Activation and inactivation are controlled by guanine nucleotide exchange factors (GEFs) that promote GDP-to-GTP exchange, and GTPase-activating proteins (GAPs) that accelerate GTP hydrolysis. Rab3GAP1/2 and GRAB are examples of such regulators in vertebrates.

Active Rab3-GTP engages effector proteins, notably Rabphilin-3A and the Rab3-interacting molecules (RIM1 and RIM2), which link Rab3 to the vesicle fusion machinery. Through these interactions, Rab3 modulates vesicle docking at the active zone, priming for SNARE-mediated fusion, and the probability of calcium-triggered exocytosis. The precise role of Rab3 can vary by tissue and isoform, and functional redundancy with other Rab proteins may occur.

In neurons, Rab3 is enriched on synaptic vesicles and participates in presynaptic vesicle cycling and neurotransmitter release. In endocrine and other secretory cells, Rab3 participates in regulated secretion from dense-core granules or secretory vesicles, contributing to secretion efficiency and timing.

Rab3-mediated pathways are studied to understand the mechanisms of synaptic transmission and hormone release, and altered Rab3 signaling has been examined in model systems to elucidate vesicle pool organization and release probability.