Gβγ acts at the C terminus of SNAP-25 to mediate presynaptic inhibition

摘要: Presynaptic inhibition mediated by G protein-coupled receptors may involve a direct interaction between proteins and the vesicle fusion machinery. The molecular target of this pathway is unknown. We demonstrate that Gbetagamma-mediated presynaptic in lamprey central synapses occurs downstream from voltage-gated Ca(2+) channels. Using microinjections botulinum toxins (BoNTs) during paired recordings, we find cleavage synaptobrevin unprimed vesicles leads to an eventual exhaustion synaptic transmission but does not prevent inhibition. In contrast, C-terminal nine amino acids 25 kDa synaptosome-associated protein (SNAP-25) BoNT A prevents Moreover, peptide containing region SNAP-25 cleaved blocks Gbetagamma inhibitory effect. Finally, removal last C-terminus weakens interactions with soluble N-ethylmaleimide-sensitive factor attachment receptor (SNARE) complexes. Thus, C terminus SNAP-25, which links synaptotagmin I SNARE complex, represent for