CALCIUM-DEPENDENT REGULATION OF RAB3 IN SHORT-TERM PLASTICITY

The Rab3 proteins are monomeric GTP-binding proteins associated with s ecretory vesicles. In their active GTP-bound state, Rab3 proteins are involved in the regulation of hormone secretion and neurotransmitter r elease. This action is thought to involve specific effecters, includin g two Ca2+-binding proteins, Rabphilin and Rim. Rab3 acts late in the exocytotic process, in a cell domain in which the intracellular Ca2+ c oncentration is susceptible to rapid changes. Therefore, we examined t he possible Ca2+-dependency of the regulatory action of GTP-bound Rab3 and wild-type Rab3 on neuroexocytosis at identified cholinergic synap ses in Aplysia californica. The effects of recombinant GTPase-deficien t Aplysia-Rab3 (apRab3-Q80L) or wild-type apRab3 were studied on evoke d acetylcholine release. Intraneuronal application of apRab3-Q80L in i dentified neurons of the buccal ganglion of Aplysia led to inhibition of neurotransmission; wild-type apRab3 was less effective. Intracellul ar chelation of Ca2+ ions by EGTA greatly potentiated the inhibitory a ction of apRab3-Q80L. Train and paired-pulse facilitation, two Ca2+-de pendent forms of short-term plasticity induced by a rise in intratermi nal 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 intracel lular Ca2+ concentration. Therefore, a Ca2+-dependent modulation of GT P-bound Rab3 function may contribute to shortterm plasticity.