Research ArticleGPCR SIGNALING

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

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Science Signaling  19 Feb 2019:
Vol. 12, Issue 569, eaat8595
DOI: 10.1126/scisignal.aat8595

Gβγ ensnares neurotransmitter vesicles

The exocytosis of neurotransmitter-containing vesicles requires the SNARE protein complex to mediate vesicle fusion with the plasma membrane. The Gβγ subunit activated by Gi/o-coupled GPCRs can inhibit this process by interacting with the SNARE protein SNAP25. Zurawski et al. generated mice that expressed a mutant form of SNAP25 that could not interact with Gβγ. These mice showed defects in nociception, stress responses, motor coordination, affect, and spatial learning. These results provide in vivo evidence of the importance of the association between presynaptic Gβγ and SNARE proteins in presynaptically inhibiting neurotransmitter release.

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