Related Experiment Video

Updated: Aug 4, 2025

Characterization of G Protein-coupled Receptors by a Fluorescence-based Calcium Mobilization Assay
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Characterization of G Protein-coupled Receptors by a Fluorescence-based Calcium Mobilization Assay

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Orphan receptor GPR158 serves as a metabotropic glycine receptor: mGlyR

Thibaut Laboute1, Stefano Zucca1, Matthew Holcomb2

  • 1Department of Neuroscience, UF Scripps Biomedical Research, Jupiter, FL 33458, USA.

Science (New York, N.Y.)
|March 30, 2023
PubMed

Insights

Researchers discovered GPR158 as a novel metabotropic glycine receptor (mGlyR). This finding reveals a new system for how glycine modulates neuronal activity, impacting cognition and affective states.

Area of Science:

  • Neuroscience
  • Molecular Biology
  • Pharmacology

Background:

  • Glycine is a key neurotransmitter in fundamental neuronal processes.
  • The metabotropic receptor for glycine's slow neuromodulatory effects remained unidentified.

Purpose of the Study:

  • To identify the orphan G protein-coupled receptor mediating glycine's metabotropic effects.
  • To elucidate the mechanism of glycine's neuromodulation via this receptor.

Main Methods:

  • G protein-coupled receptor (GPCR) identification.
  • Ligand binding assays using glycine and taurine.
  • Inhibition assays of the regulator of G protein signaling 7-G protein β5 (RGS7-Gβ5) complex.
  • Measurement of adenosine 3',5'-monophosphate (cAMP) production.
  • Assessment of neuronal excitability in cortical neurons.

Main Results:

  • GPR158 was identified as a metabotropic glycine receptor (mGlyR).
  • Glycine and taurine bind to GPR158's Cache domain, inhibiting RGS7-Gβ5 activity.
  • Glycine signaling via mGlyR suppresses cAMP production.
  • Glycine, but not taurine, modulates cortical neuron excitability through mGlyR.

Conclusions:

  • GPR158 functions as a metabotropic glycine receptor (mGlyR).
  • This discovery unveils a significant neuromodulatory system for glycine.
  • Findings have implications for understanding cognition and affective states.

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