Orphan receptor GPR158 serves as a metabotropic glycine receptor: mGlyR

Autor: Thibaut Laboute, Stefano Zucca, Matthew Holcomb, Dipak N. Patil, Chris Garza, Brittany A. Wheatley, Raktim N. Roy, Stefano Forli, Kirill A. Martemyanov
Rok vydání: 2023
Předmět:
Zdroj: Science. 379:1352-1358
ISSN: 1095-9203
0036-8075
Popis: 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 β5 (RGS7-Gβ5), 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.
Databáze: OpenAIRE
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