Modulation of neurotransmitter exocytosis by activated Gi/o coupled G-protein coupled receptors (GPCRs) is a universal regulatory mechanism used both to avoid overstimulation and to influence circuitry. One of the known modulation mechanisms is the interaction between Gβγ and the soluble N-ethylmaleimide-sensitive factor attachment protein receptor (SNAREs). There are 5 Gβ and 12 Gγ subunits, but specific Gβγs activated by a given GPCR and the specificity to effectors, such as SNARE, in vivo are not known. Although less studied, Gβγ binding to the exocytic fusion machinery (i.e. SNARE) provides a more direct regulatory mechanism for neurotransmitter release. Here, we review some recent insights in the architecture of the synaptic terminal, modulation of synaptic transmission, and implications of G protein modulation of synaptic transmission in diseases. Numerous presynaptic proteins are involved in the architecture of synaptic terminals, particularly the active zone, and their importance in the regulation of exocytosis is still not completely understood. Further understanding of the Gβγ-SNARE interaction and the architecture and mechanisms of exocytosis may lead to the discovery of novel therapeutic targets to help patients with various disorders such as hypertension, attention-deficit/hyperactivity disorder, post-traumatic stress disorder, and acute/chronic pain.
Keywords: Calcium; Exocytosis; G protein; GPCR; SNARE; Secretion.
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