Orphan receptor GPR158 serves as a metabotropic glycine receptor: mGlyR

• 成果类型: Article
• 署名作者: Laboute, Thibaut; Zucca, Stefano; Holcomb, Matthew; Patil, Dipak N.; Garza, Chris; Wheatley, Brittany A.; Roy, Raktim N.; Forli, Stefano; Martemyanov, Kirill A.
• 署名单位: State University System of Florida; University of Florida; Herbert Wertheim UF Scripps Institute for Biomedical Innovation & Technology; Scripps Research Institute; State University System of Florida; University of Florida; Herbert Wertheim UF Scripps Institute for Biomedical Innovation & Technology; Eli Lilly
• 刊物名称: SCIENCE
• ISSN/ISSBN: 0036-12537
• DOI: 10.1126/science.add7150
• 发表日期: 2023-03-31
• 页码: 1352-1357
• 关键词: g-proteins; taurine; inhibition; complexes

摘要

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 b5 (RGS7-Gb5), 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.