Disabling the Gβγ-SNARE interaction disrupts GPCR-mediated presynaptic inhibition, leading to physiological and behavioral phenotypes.

ABSTRACT: G protein-coupled receptors (GPCRs) that couple to G_i/o proteins modulate neurotransmission presynaptically by inhibiting exocytosis. Release of Gβγ subunits from activated G proteins decreases the activity of voltage-gated Ca²⁺ channels (VGCCs), decreasing excitability. A less understood Gβγ-mediated mechanism downstream of Ca²⁺ entry is the binding of Gβγ to SNARE complexes, which facilitate the fusion of vesicles with the cell plasma membrane in exocytosis. Here, we generated mice expressing a form of the SNARE protein SNAP25 with premature truncation of the C terminus and that were therefore partially deficient in this interaction. SNAP25Δ3 homozygote mice exhibited normal presynaptic inhibition by GABA_B receptors, which inhibit VGCCs, but de

SUBMITTER: Zurawski Z 

PROVIDER: S-EPMC7758873 | biostudies-literature | 2019 Feb

REPOSITORIES: biostudies-literature