NMDA Receptors.

One of the major classes of ionotropic glutamate receptors is made up of the N-methyl-D-aspartate (NMDA) receptors, which require two agonists, glycine and glutamate, for activation and can pass calcium ions that may mediate synaptic and neuronal plasticity. They are formed from complexes made by various combinations of the subunits NR1 (with eight isoforms), NR2A-D, and NR3A-B and are found in most neurons of the brain and in various other cells. During development, generally NMDA receptors with NR2B, NR2D, and NR3A are abundant and decrease during maturation, whereas those with NR2A and NR2C increase. The function of NMDA receptors has been explored with a wide range of in vitro and in vivo studies, employing both recombinant gene constructs and native receptors. NMDA receptor subunits contain various motifs that control retention in the endoplasmic reticulum and trafficking through Golgi and other organelles to reach the cell membrane. Association of NMDA receptors with PDZ domain-containing proteins such as PSD-95 and SAP102 may be particularly important to trafficking and/or stabilization and function on the cell membrane. NMDA receptors on the cell membrane are sequestered mainly to the postsynaptic membrane of synapses, but some populations remain in extrasynaptic domains, especially those receptors that contain NR2B or NR2D. [ABSTRACT FROM AUTHOR]