A Presynaptic Group III mGluR Recruits G??/SNARE Interactions to Inhibit Synaptic Transmission by Cone Photoreceptors in the Vertebrate Retina.

ABSTRACT: G-protein ?? subunits (G??) 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 G?? contributes to these effects. We tested whether activation of one particular GPCR, a metabotropic glutamate receptor (mGluR), can reduce cone synaptic transmission via G?? 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 and G?? 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-25 C terminus. Introducing G?? subunits directly into cones reduced EPSC amplitude. This effect was inhibited by BoNT/A, supporting a role for G??/SNAP-25 interactions. However, the mGluR-dependent reduction in ICa was not mimicked by G??, indicating that this effect was independent of G??. The finding that synaptic transmission at cone ribbon synapses is regulated by G??/SNAP-25 interactions indicates that these mechanisms are shared by conventional and ribbon-type synapses. G?? liberated from other photoreceptor GPCRs is also likely to regulate synaptic transmission.SIGNIFICANCE STATEMENT Dynamic regulation of synaptic transmission by presynaptic G-protein coupled receptors shapes information flow through neural circuits. At the first synapse in the visual system, presynaptic metabotropic glutamate receptors (mGluRs) regulate cone photoreceptor synaptic transmission, although the mechanisms and functional impact of this are unclear. We show that mGluRs regulate light response encoding across the cone synapse, accomplished in part by triggering G-protein ?? subunits (G??) interactions with SNAP-25, a core component of the synaptic vesicle fusion machinery. In addition to revealing a role in visual processing, this provides the first demonstration that G??/SNAP-25 interactions regulate synaptic function at a ribbon-type synapse, contributing to an emerging picture of the ubiquity of G??/SNARE interactions in regulating synaptic transmission throughout the nervous system.

SUBMITTER: Van Hook MJ 

PROVIDER: S-EPMC5413191 | biostudies-literature | 2017 Apr

REPOSITORIES: biostudies-literature