NR1/A0001

NR1 is the obligatory subunit of NMDA receptors.

NR1, also known as A0001, is a subunit of the transmembrane N-methyl-D-aspartate receptor (NMDAR), an important glutamate-gated ion channel expressed mostly in neurons. NMDARs are ligand- and voltage-gated ion channels that mediate glutamate neurotransmission and play key roles in synaptic plasticity, synaptogenesis, excitotoxicity, learning and memory. NR1 knock-out mouse die perinatally but tissue-specific knock-out only impairs special learning, memory, and long-term potentiation (LTP) in the hippocampus. Feeding mice NMDAR-specific inhibitors impairs learning and memory and prevents LTP. NR1 requires the NR2 subunit to leave the endoplasmic reticulum. NR1 is localized largely at post-synaptic membranes and densities. There are on average 8-20 molecules of NR1 per synapse. There is also evidence of extra-synaptic and presynaptic localization. NR1 is composed of an extracellular ligand-binding domain, transmembrane domains, and an intracellular C-terminal domain. The NR1 intracellular domain is over 100 amino acids long and contains numerous protein-protein interaction sites and phosphorylation and dephosphorylation sites. The extra cellular domain contains disulphide bridges that bind with the NR2 subunit. NR1 has direct protein-protein interactions with DLG4, MPDZ, and dopamine receptor D1 and is homologous with other ionotropic glutamate receptors (including alpha-amino-3-hydroxy-5-methyl-4-isoxazolepropionic acid (AMPA) and kainate receptors). NR1 mediates excitotoxicity in stroke and is also associated with Alzheimer’s disease, schizophrenia, epilepsy and pain sensation.