| First Author | Laboute T | Year | 2023 |
| Journal | Science | Volume | 379 |
| Issue | 6639 | Pages | 1352-1358 |
| PubMed ID | 36996198 | Mgi Jnum | J:335122 |
| Mgi Id | MGI:7466434 | Doi | 10.1126/science.add7150 |
| Citation | Laboute T, et al. (2023) Orphan receptor GPR158 serves as a metabotropic glycine receptor: mGlyR. Science 379(6639):1352-1358 |
| abstractText | Glycine is a major neurotransmitter involved in several fundamental neuronal processes. The identity of the metabotropic receptor mediating slow neuromodulatory effects of glycine is unknown. We identified an orphan G protein-coupled receptor, GPR158, as a metabotropic glycine receptor (mGlyR). Glycine and a related modulator, taurine, directly bind to a Cache domain of GPR158, and this event inhibits the activity of the intracellular signaling complex regulator of G protein signaling 7-G protein beta5 (RGS7-Gbeta5), which is associated with the receptor. Glycine signals through mGlyR to inhibit production of the second messenger adenosine 3',5'-monophosphate. We further show that glycine, but not taurine, acts through mGlyR to regulate neuronal excitability in cortical neurons. These results identify a major neuromodulatory system involved in mediating metabotropic effects of glycine, with implications for understanding cognition and affective states. |
