PT  - JOURNAL ARTICLE
AU  - Zack Zurawski
AU  - Analisa D. Thompson Gray
AU  - Lillian J. Brady
AU  - Brian Page
AU  - Emily Church
AU  - Nicholas A. Harris
AU  - Michael R. Dohn
AU  - Yun Young Yim
AU  - Karren Hyde
AU  - Douglas P. Mortlock
AU  - Danny G. Winder
AU  - Simon Alford
AU  - Carrie K. Jones
AU  - Heidi E. Hamm
TI  - Disabling Gβγ SNARE interaction in transgenic mice disrupts GPCR-mediated presynaptic inhibition leading to physiological and behavioral phenotypes
AID  - 10.1101/280347
DP  - 2018 Jan 01
TA  - bioRxiv
PG  - 280347
4099  - http://biorxiv.org/content/early/2018/03/11/280347.short
4100  - http://biorxiv.org/content/early/2018/03/11/280347.full
AB  - Gi/o-coupled G-protein coupled receptors modulate neurotransmission presynaptically through inhibition of exocytosis. Release of Gβγ subunits decreases the activity of voltage-gated calcium channels (VGCC), decreasing excitability. A less understood Gβγ–mediated mechanism downstream of calcium entry is the binding of Gβγ to SNARE complexes. Here, we create a mouse partially deficient in this interaction. SNAP25Δ3 homozygote animals are developmentally normalbut impaired gait and supraspinal nociception. They also have elevated stress-induced hyperthermia and impaired inhibitory postsynaptic responses to α2A-AR, but normal inhibitory postsynaptic responses to Gi/o-coupled GABAB receptor activation. SNAP25Δ3 homozygotes have deficits in inhibition of hippocampal postsynaptic responses to 5 HT1b agonists that affect hippocampal learning. These data suggest that Gi/o-coupled GPCR inhibition of exocytosis through the Gβγ-SNARE interaction is a crucial component of numerous physiological and behavioral processes.