Structural highlights
Function
MGLYR_HUMAN Metabotropic receptor for glycine that controls synapse formation and function in the brain (PubMed:36996198). Acts as an atypical G-protein coupled receptor that recruits and regulates the RGS7-GNB5 complex instead of activating G proteins (PubMed:31189666, PubMed:36996198). In absence of glycine ligand, promotes the GTPase activator activity of RGS7, increasing the GTPase activity of G protein alpha subunits, thereby driving them into their inactive GDP-bound form (PubMed:36996198). Glycine-binding changes the conformation of the intracellular surface, inhibiting the GTPase activator activity of the RGS7-GNB5 complex, promoting G protein alpha subunits into their active GTP-bound form and regulating cAMP levels (PubMed:36996198). Also able to bind taurine, a compound closely related to glycine, but with a two-fold lower affinity (PubMed:36996198). Glycine receptor-dependent regulation of cAMP controls key ion channels, kinases and neurotrophic factors involved in neuronal excitability and synaptic transmission (PubMed:36996198). Plays a pivotal role in regulating mood and cognition via its ability to regulate neuronal excitability in L2/L3 pyramidal neurons of the prefrontal cortex (By similarity). Also involved in spatial learning by regulating hippocampal CA1 neuronal excitability (By similarity). Acts as a synaptic organizer in the hippocampus, required for proper mossy fiber-CA3 neurocircuitry establishment, structure and function: induces presynaptic differentiation in contacting axons via its interaction with GPC4 (By similarity). In addition to glycine, may also act as a receptor for osteocalcin (BGLAP) hormone: osteocalcin-binding initiates a signaling response that prevents neuronal apoptosis in the hippocampus and regulates the synthesis of neurotransmitters (By similarity).[UniProtKB:Q8C419][1] [2]
References
- ↑ Hajj M, De Vita T, Vol C, Renassia C, Bologna JC, Brabet I, Cazade M, Pastore M, Blahos J, Labesse G, Pin JP, Prézeau L. Nonclassical Ligand-Independent Regulation of Go Protein by an Orphan Class C G-Protein-Coupled Receptor. Mol Pharmacol. 2019 Aug;96(2):233-246. PMID:31189666 doi:10.1124/mol.118.113019
- ↑ Laboute T, Zucca S, Holcomb M, Patil DN, Garza C, Wheatley BA, Roy RN, Forli S, Martemyanov KA. Orphan receptor GPR158 serves as a metabotropic glycine receptor: mGlyR. Science. 2023 Mar 31;379(6639):1352-1358. PMID:36996198 doi:10.1126/science.add7150
