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Neurochemical Research

, Volume 44, Issue 3, pp 636–649 | Cite as

Gβγ SNARE Interactions and Their Behavioral Effects

  • Simon AlfordEmail author
  • Heidi Hamm
  • Shelagh Rodriguez
  • Zack Zurawski
Original Paper

Abstract

Presynaptic terminals possess interlocking molecular mechanisms that control exocytosis. An example of such complexity is the modulation of release by presynaptic G Protein Coupled Receptors (GPCRs). GPCR ubiquity at synapses—GPCRs are present at every studied presynaptic terminal—underlies their critical importance in synaptic function. GPCRs mediate presynaptic modulation by mechanisms including via classical Gα effectors, but membrane-delimited actions of Gβγ can also alter probability of release by altering presynaptic ionic conductances. This directly or indirectly modifies action potential-evoked presynaptic Ca2+ entry. In addition, Gβγ can interact directly with SNARE complexes responsible for synaptic vesicle fusion to reduce peak cleft neurotransmitter concentrations during evoked release. The interaction of Gβγ with SNARE is displaced via competitive interaction with C2AB-domain containing calcium sensors such as synaptotagmin I in a Ca2+-sensitive manner, restoring exocytosis. Synaptic modulation of this form allows selective inhibition of postsynaptic receptor-mediated responses, and this, in combination with Ca2+ sensitivity of Gβγ effects on SNARE complexes allows for specific behavioral outcomes. One such outcome mediated by 5-HT receptors in the spinal cord seen in all vertebrates shows remarkable synergy between presynaptic effects of Gβγ and postsynaptic 5-HT-mediated changes in activation of Ca2+-dependent K+ channels. While acting through entirely separate cellular compartments and signal transduction pathways, these effects converge on the same effect on locomotion and other critical functions of the central nervous system.

Keywords

G proteins Presynaptic Serotonin Locomotion Presynaptic inhibition Short term plasticity 

Notes

Acknowledgements

We would like to thank Dr Ed Chapman, University of Wisconsin, Madison for advice on liposomal fusion, and Dr Réjean Dubuc, Université de Montréal for advice on brainstem evoked locomotor behavior.

Funding

Funding was provided by the following R01 grants NIH (NIMH) R01MH101679 to Heidi Hamm and RO1MH084874 to Simon Alford.

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© Springer Science+Business Media, LLC, part of Springer Nature 2018

Authors and Affiliations

  1. 1.Department of Anatomy and Cell BiologyUniversity of Illinois at ChicagoChicagoUSA
  2. 2.Department of PharmacologyVanderbilt University Medical CenterNashvilleUSA

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