Glutamate ionotropic receptor NMDA type subunit 1 glycine binding site (GluN1 glycine site)

The Glutamate ionotropic receptor NMDA type subunit 1 (GRIN1) glycine binding site is a fundamental regulatory component of the N-methyl-D-aspartate (NMDA) receptor, a primary excitatory neurotransmitter receptor in the mammalian brain (UniProt P35222). Unlike most ligand-gated ion channels, the NMDA receptor is a co-agonist-dependent channel, requiring the simultaneous occupancy of the glutamate site on the GluN2 subunit and the glycine site on the GluN1 subunit to permit ion flow (PubMed: 15312400). This site is often termed the strychnine-insensitive glycine site to distinguish it from the inhibitory glycine receptors found primarily in the spinal cord. It plays a critical role in mediating synaptic plasticity and long-term potentiation, which are the cellular hallmarks of learning and memory (PubMed: 24331069). Clinically, this site is a major therapeutic target; NMDA receptor hypofunction at this site is linked to the cognitive and negative symptoms of schizophrenia, leading to the development of glycine site agonists and partial agonists like D-cycloserine (PubMed: 17982250). Conversely, glycine site antagonists have been explored for their potential to mitigate excitotoxic neuronal death in stroke and to treat chronic pain by reducing central sensitization (PubMed: 21496568).

Other names

NR1 glycine siteGlycine-B siteStrychnine-insensitive glycine binding siteNMDA receptor glycine co-agonist siteGRIN1 glycine site

Co-agonist modulation of NMDA receptor activity; binding of glycine or D-serine to this site is required for glutamate-induced channel opening.