A presynaptic group III mGluR recruits Gβγ/SNARE interactions to inhibit synaptic transmission by cone photoreceptors in the vertebrate retina

Matthew Van Hook, Norbert Babai, Zack Zurawski, Yun Young Yim, Heidi E. Hamm, Wallace B Thoreson

Research output: Contribution to journalArticle

7 Scopus citations

Abstract

G-protein βγ subunits (Gβγ) interact with presynaptic proteins and regulate neurotransmitter release downstream of Ca2+ influx. To accomplish their roles in sensory signaling, photoreceptor synapses use specialized presynaptic proteins that support neurotransmission at active zone structures known as ribbons. While several G-protein coupled receptors (GPCRs) influence synaptic transmission at ribbon synapses of cones and other retinal neurons, it is unknown whether Gβγ contributes to these effects.Wetested whether activation of one particular GPCR, a metabotropic glutamate receptor (mGluR), can reduce cone synaptic transmission via Gβγ in tiger salamander retinas. In recordings from horizontal cells, we found that an mGluR agonist (L-AP4) reduced cone-driven light responses and mEPSC frequency. In paired recordings of cones and horizontal cells, L-AP4 slightly reduced cone ICa (~10%) and caused a larger reduction in cone-driven EPSCs (~30%). Proximity ligation assay revealed direct interactions between SNAP-25 andGβγ subunits in retinal synaptic layers. Pretreatment with the SNAP-25 cleaving protease BoNT/A inhibited L-AP4 effects on synaptic transmission, as did introduction of a peptide derived from the SNAP-25Cterminus. IntroducingGβγ subunits directly into cones reduced EPSC amplitude. This effect was inhibited by BoNT/A, supporting a role for Gβγ/SNAP-25 interactions. However, the mGluR-dependent reduction in ICa was not mimicked by Gβγ, indicating that this effect was independent of Gβγ. The finding that synaptic transmission at cone ribbon synapses is regulated by Gβγ/SNAP-25 interactions indicates that these mechanisms are shared by conventional and ribbon-type synapses. Gβγ liberated from other photoreceptor GPCRs is also likely to regulate synaptic transmission.

Original languageEnglish (US)
Pages (from-to)4618-4634
Number of pages17
JournalJournal of Neuroscience
Volume37
Issue number17
DOIs
Publication statusPublished - Apr 26 2017

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Keywords

  • G-protein coupled receptor
  • Retina
  • Ribbon
  • SNARE complex
  • Synapse
  • mGluR

ASJC Scopus subject areas

  • Neuroscience(all)

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