Calcium-dependent regulation of rab3 in short-term plasticity.

The Rab3 proteins are monomeric GTP-binding proteins associated with secretory vesicles. In their active GTP-bound state, Rab3 proteins are involved in the regulation of hormone secretion and neurotransmitter release. This action is thought to involve specific effectors, including two Ca2+-binding proteins, Rabphilin and Rim. Rab3 acts late in the exocytotic process, in a cell domain in which the intracellular Ca2+ concentration is susceptible to rapid changes. Therefore, we examined the possible Ca2+-dependency of the regulatory action of GTP-bound Rab3 and wild-type Rab3 on neuroexocytosis at identified cholinergic synapses in Aplysia californica. The effects of recombinant GTPase-deficient Aplysia-Rab3 (apRab3-Q80L) or wild-type apRab3 were studied on evoked acetylcholine release. Intraneuronal application of apRab3-Q80L in identified neurons of the buccal ganglion of Aplysia led to inhibition of neurotransmission; wild-type apRab3 was less effective. Intracellular chelation of Ca2+ ions by EGTA greatly potentiated the inhibitory action of apRab3-Q80L. Train and paired-pulse facilitation, two Ca2+-dependent forms of short-term plasticity induced by a rise in intraterminal Ca2+ concentration, were increased after injection of apRab3-Q80L. This result suggests that the inhibition exerted by GTP-bound Rab3 on neuroexocytosis is reduced during transient augmentations of intracellular Ca2+ concentration. Therefore, a Ca2+-dependent modulation of GTP-bound Rab3 function may contribute to short-term plasticity.