GTP-binding proteins: necessary components of the presynaptic terminal for synaptic transmission and its modulation

Using synapses that form between somata of Helisoma neurons in cell culture, we have studied the presynaptic regulation of synaptic transmission. Guanosine 5'-triphosphate (GTP)-binding proteins play critical roles in regulating synaptic transmission. Injection of guanine nucleotide analogues has demonstrated that one or more GTP-binding protein is necessary for transmitter release. Heterotrimeric G proteins continuously regulate the amount of transmitter released at the synapse by modulating potassium and calcium channels, and by controlling the secretory response to calcium. Perturbations of the synapse using guanosine 5'-diphosphate (GDP) beta S, GTP gamma S, and rab effector domain peptides suggest that small GTP-binding proteins also play critical roles in the synapse. We discuss the possibility that rab3, or related proteins, are required for exocytosis, and by cooperating with other proteins maintain vesicles in a docked state in the synapse.