A metabotropic receptor for glycine

The molecular identity of the receptor that mediates the slower, neuromodulatory effects of glycine is not clear. Laboute et al. now show that the orphan G-protein-coupled receptor GPR158 acts as a metabotropic glycine receptor (mGlyR) to convey such effects.

GPR158 is expressed in the mammalian brain, but its ligand was unknown. The authors noticed that GPR158’s extracellular cache ___domain contained a small pocket that resembled amino acid-binding pockets in other such domains. They screened a library of amino acids in a cell-line-based assay to see whether any could alter GPR158-mediated signalling and found that glycine elicited a decrease in cAMP levels.