9pzt

Structural highlights

Function

NMDE1_MOUSE Component of N-methyl-D-aspartate (NMDA) receptors (NMDARs) that function as heterotetrameric, ligand-gated cation channels with high calcium permeability and voltage-dependent block by Mg(2+) (PubMed:12008020, PubMed:1374164). NMDARs participate in synaptic plasticity for learning and memory formation by contributing to the slow phase of excitatory postsynaptic current, long-term synaptic potentiation, and learning (PubMed:7816096, PubMed:8987814). Channel activation requires binding of the neurotransmitter L-glutamate to the GluN2 subunit, glycine or D-serine binding to the GluN1 subunit, plus membrane depolarization to eliminate channel inhibition by Mg(2+) (PubMed:12008020, PubMed:1374164, PubMed:7790891). NMDARs mediate simultaneously the potasium efflux and the influx of calcium and sodium (By similarity). Each GluN2 subunit confers differential attributes to channel properties, including activation, deactivation and desensitization kinetics, pH sensitivity, Ca2(+) permeability, and binding to allosteric modulators (PubMed:10436042, PubMed:12008020). Participates in the synaptic plasticity regulation through activation by the L-glutamate releaseed by BEST1, into the synaptic cleft, upon F2R/PAR-1 activation in astrocyte (PubMed:25645137).[UniProtKB:P35438]^{[1] [2] [3] [4] [5] [6] [7]}

References

1. ↑ Chen N, Luo T, Raymond LA. Subtype-dependence of NMDA receptor channel open probability. J Neurosci. 1999 Aug 15;19(16):6844-54. PMID:10436042 doi:10.1523/JNEUROSCI.19-16-06844.1999
2. ↑ Matsuda K, Kamiya Y, Matsuda S, Yuzaki M. Cloning and characterization of a novel NMDA receptor subunit NR3B: a dominant subunit that reduces calcium permeability. Brain Res Mol Brain Res. 2002 Apr 30;100(1-2):43-52. PMID:12008020 doi:10.1016/s0169-328x(02)00173-0
3. ↑ Meguro H, Mori H, Araki K, Kushiya E, Kutsuwada T, Yamazaki M, Kumanishi T, Arakawa M, Sakimura K, Mishina M. Functional characterization of a heteromeric NMDA receptor channel expressed from cloned cDNAs. Nature. 1992 May 7;357(6373):70-4. PMID:1374164 doi:10.1038/357070a0
4. ↑ Park H, Han KS, Seo J, Lee J, Dravid SM, Woo J, Chun H, Cho S, Bae JY, An H, Koh W, Yoon BE, Berlinguer-Palmini R, Mannaioni G, Traynelis SF, Bae YC, Choi SY, Lee CJ. Channel-mediated astrocytic glutamate modulates hippocampal synaptic plasticity by activating postsynaptic NMDA receptors. Mol Brain. 2015 Feb 3;8:7. PMID:25645137 doi:10.1186/s13041-015-0097-y
5. ↑ Matsui T, Sekiguchi M, Hashimoto A, Tomita U, Nishikawa T, Wada K. Functional comparison of D-serine and glycine in rodents: the effect on cloned NMDA receptors and the extracellular concentration. J Neurochem. 1995 Jul;65(1):454-8. PMID:7790891 doi:10.1046/j.1471-4159.1995.65010454.x
6. ↑ Sakimura K, Kutsuwada T, Ito I, Manabe T, Takayama C, Kushiya E, Yagi T, Aizawa S, Inoue Y, Sugiyama H, et al.. Reduced hippocampal LTP and spatial learning in mice lacking NMDA receptor epsilon 1 subunit. Nature. 1995 Jan 12;373(6510):151-5. PMID:7816096 doi:10.1038/373151a0
7. ↑ Kadotani H, Hirano T, Masugi M, Nakamura K, Nakao K, Katsuki M, Nakanishi S. Motor discoordination results from combined gene disruption of the NMDA receptor NR2A and NR2C subunits, but not from single disruption of the NR2A or NR2C subunit. J Neurosci. 1996 Dec 15;16(24):7859-67. PMID:8987814 doi:10.1523/JNEUROSCI.16-24-07859.1996