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.
Doussau
F
F
Laboratoire de Neurobiologie Cellulaire, UPR 9009, Centre National de la Recherche Scientifique, F-67084 Strasbourg Cedex, France.
Clabecq
A
A
Henry
J P
JP
Darchen
F
F
Poulain
B
B
D000109:Acetylcholine / Q000378:metabolism; D000818:Animals; D001048:Aplysia; D002118:Calcium / Q000502:physiology*; D005089:Exocytosis / Q000502:physiology*; D020558:GTP Phosphohydrolases / Q000172:deficiency; D019204:GTP-Binding Proteins / Q000502:physiology*; D008845:Microinjections; D009419:Nerve Tissue Proteins / Q000502:physiology*; D009473:Neuronal Plasticity / Q000502:physiology*; D018408:Patch-Clamp Techniques; D011994:Recombinant Proteins / Q000494:pharmacology; D013997:Time Factors; D020692:rab3 GTP-Binding Proteins
D009419:Nerve Tissue Proteins; D011994:Recombinant Proteins; D020558:GTP Phosphohydrolases; D019204:GTP-Binding Proteins; D020692:rab3 GTP-Binding Proteins; D000109:Acetylcholine; D002118:Calcium