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Grin2a  -  glutamate receptor, ionotropic, N-methyl D...

Rattus norvegicus

Synonyms: GluN2A, Glutamate receptor ionotropic, NMDA 2A, N-methyl D-aspartate receptor subtype 2A, NMDAR2A, NR2A
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Disease relevance of Grin2a


Psychiatry related information on Grin2a


High impact information on Grin2a

  • Two regions in the D1 receptor carboxyl tail can directly and selectively couple to NMDA glutamate receptor subunits NR1-1a and NR2A [8].
  • By co-immunoprecipitation with subunit-specific antibodies, we present here direct evidence that NMDA receptors exist in rat neocortex as heteromeric complexes of considerable heterogeneity, some containing both NR2A and NR2B subunits [9].
  • Differential roles of NR2A- and NR2B-containing NMDA receptors in Ras-ERK signaling and AMPA receptor trafficking [10].
  • AMPA receptor-dependent clustering of synaptic NMDA receptors is mediated by Stargazin and NR2A/B in spinal neurons and hippocampal interneurons [11].
  • The apparent affinity for Zn2+ of the heteromeric NMDA receptors is determined by the subtype of NR2 subunit expressed, with NR2A-containing receptors being the most sensitive (IC50, approximately 20 nM) and NR2C-containing receptors being the least sensitive (IC50, approximately 30 microM) [12].

Chemical compound and disease context of Grin2a


Biological context of Grin2a


Anatomical context of Grin2a

  • NMDA receptors in the lateral thalamus (with a high density of NR2A subunit mRNA) displayed higher affinity for antagonists and a lower affinity for agonists than did NMDA receptors of the medial striatum (a region rich in NR2B mRNA) [17].
  • NMDAR2A and NMDAR2C expressed individually in Xenopus oocytes showed no electrophysiological response to agonists [21].
  • Treatment of rat brain slices with Tat-H-Ras depleted NR2A from the synaptic membrane, decreased endogenous Src activity and NR2A phosphorylation, and decreased the magnitude of hippocampal LTP [20].
  • Our results show that SAP97 directly interacts with the NR2A subunit of NMDA receptor both in an in vitro "pull-out" assay and in co-immunoprecipitation experiments from homogenates and synaptosomes purified from hippocampal rat tissue [19].
  • Specifically, within the ipsilateral hippocampus, NR2A was reduced by 9.9%, 47.9%, 40.8%, and 6.3% on PID1, PID2, PID4, and PID7, respectively [22].

Associations of Grin2a with chemical compounds

  • This antibody (NR2A/B) did not cross-react with extracts from transfected cells expressing other glutamate receptor subunits, nor did it label non-neuronal tissues [23].
  • The effectiveness of the C1 exon to reduce the higher form of potentiation is modulated by heteromeric assemblies with NR2A heteromers yielding smaller levels of potentiation and a larger C1 exon effect compared with NR2B heteromers [24].
  • Cotransfection of H-Ras and Src inhibited Src activity and decreased NR2A tyrosine phosphorylation [20].
  • Some of the effects of cyanide on NR1/NR2B receptors may be mediated by the formation of a thiocyanate adduct with a cysteine residue located in NR1 [25].
  • In addition, the activity of alphaCaMKII on exogenous substrates, such as syntide-2, and the phosphorylation of NR2A/B subunits of N-Methyl-D-Aspartate receptor was reduced in hippocampal post-synaptic densities of streptozotocin-diabetic rats as compared with control rats [26].
  • Whole cell voltage-clamp recordings show that Zn(2+) inhibition of agonist-evoked NMDA receptor currents of NR1/NR2A-transfected HEK 293 cells and cultured cortical neurons is significantly reduced by plasmin treatment [27].

Physical interactions of Grin2a

  • In contrast, the NR2A subunit localizes to the synapse in the absence of PDZ binding and is not altered by mutations in its motif corresponding to YEKL of NR2B [28].
  • Accordingly, alphaCaMKII(1-325) competes with both the native PSD-95 and the native kinase itself for the binding to NR2A [29].

Regulatory relationships of Grin2a

  • In culture, 25 mM KCl or NMDA rapidly induced NR2A and downregulated NR2B, followed by gradual induction of NR2C [18].
  • We showed previously in the somatosensory cortex that the shortening of NMDA receptor kinetics correlates with a developmentally-regulated increase in the NR2A subunit expression [6].
  • Only a fraction (approximately 23%) of the SAP102 clusters expressed NR2A, suggesting SAP102 is also associated with other subunits or receptors [30].
  • The incubation of PSD with BDNF and NGF induced the phosphorylation of NR2A and B subunits [31].
  • In addition, Ser/Ala1289 and Ser/Asp1289 point mutations on the unique CaMKII phosphosite of NR2A did not significantly influence the binding of native alphaCaMKII and PSD-95 to the NR2A C-tail [29].

Other interactions of Grin2a

  • In 5 mM KCl, a similar, rapid increase in NR2A was observed, but disappearance of NR2B occurred over a longer time course [18].
  • In the cerebellum, in contrast to staining with NR1 antibody, Purkinje cell staining with NR2A/B antibody was low, indicating that these neurons may lack functional NMDA receptors [23].
  • Last but not least, in choline acetyltransferase (ChAT)-positive striatal interneurons of PND 14 and adult rats, levels of NR1 and NR2A immunoreactivity was seen to increase [32].
  • In addition, double immunofluorescence revealed that the levels of NR1 immunoreactivity increased but the levels of NR2A immunoreactivity were the same in parvalbumin (PV)-positive striatal interneurons of PND 14 and adult rats [32].
  • One day following washout, it was observed that PCP treatment caused an increase in NR1, NR2A and Bax polypeptides in the cortex, but had no effect on Bcl-xL [33].

Analytical, diagnostic and therapeutic context of Grin2a


  1. Inhibition of protein kinase C reduces ischemia-induced tyrosine phosphorylation of the N-methyl-d-aspartate receptor. Cheung, H.H., Teves, L., Wallace, M.C., Gurd, J.W. J. Neurochem. (2003) [Pubmed]
  2. Activation of NMDA receptors and L-type voltage-gated calcium channels mediates enhanced formation of Fyn-PSD95-NR2A complex after transient brain ischemia. Hou, X.Y., Zhang, G.Y., Yan, J.Z., Chen, M., Liu, Y. Brain Res. (2002) [Pubmed]
  3. Increased NR1-NR2A/B coassembly as a mechanism for rat chronic hippocampal epilepsy. Mikuni, N., Babb, T.L., Christi, W. Neurosci. Lett. (1999) [Pubmed]
  4. Injury-induced alterations in N-methyl-D-aspartate receptor subunit composition contribute to prolonged 45calcium accumulation following lateral fluid percussion. Osteen, C.L., Giza, C.C., Hovda, D.A. Neuroscience (2004) [Pubmed]
  5. Repetitive febrile seizures in rat pups cause long-lasting deficits in synaptic plasticity and NR2A tyrosine phosphorylation. Chang, Y.C., Kuo, Y.M., Huang, A.M., Huang, C.C. Neurobiol. Dis. (2005) [Pubmed]
  6. Genetic and epigenetic regulation of NMDA receptor expression in the rat visual cortex. Nase, G., Weishaupt, J., Stern, P., Singer, W., Monyer, H. Eur. J. Neurosci. (1999) [Pubmed]
  7. Differential effects of electroconvulsive shock on the glutamate receptor mRNAs for NR2A, NR2B and mGluR5b. Watkins, C.J., Pei, Q., Newberry, N.R. Brain Res. Mol. Brain Res. (1998) [Pubmed]
  8. Dual regulation of NMDA receptor functions by direct protein-protein interactions with the dopamine D1 receptor. Lee, F.J., Xue, S., Pei, L., Vukusic, B., Chéry, N., Wang, Y., Wang, Y.T., Niznik, H.B., Yu, X.M., Liu, F. Cell (2002) [Pubmed]
  9. Changing subunit composition of heteromeric NMDA receptors during development of rat cortex. Sheng, M., Cummings, J., Roldan, L.A., Jan, Y.N., Jan, L.Y. Nature (1994) [Pubmed]
  10. Differential roles of NR2A- and NR2B-containing NMDA receptors in Ras-ERK signaling and AMPA receptor trafficking. Kim, M.J., Dunah, A.W., Wang, Y.T., Sheng, M. Neuron (2005) [Pubmed]
  11. AMPA receptor-dependent clustering of synaptic NMDA receptors is mediated by Stargazin and NR2A/B in spinal neurons and hippocampal interneurons. Mi, R., Sia, G.M., Rosen, K., Tang, X., Moghekar, A., Black, J.L., McEnery, M., Huganir, R.L., O'Brien, R.J. Neuron (2004) [Pubmed]
  12. Four residues of the extracellular N-terminal domain of the NR2A subunit control high-affinity Zn2+ binding to NMDA receptors. Fayyazuddin, A., Villarroel, A., Le Goff, A., Lerma, J., Neyton, J. Neuron (2000) [Pubmed]
  13. Tyrosine kinase and tyrosine phosphatase participate in regulation of interactions of NMDA receptor subunit 2A with Src and Fyn mediated by PSD-95 after transient brain ischemia. Chen, M., Hou, X., Zhang, G. Neurosci. Lett. (2003) [Pubmed]
  14. Expression of ionotropic glutamate receptor subunits in glial cells of the hippocampal CA1 area following transient forebrain ischemia. Gottlieb, M., Matute, C. J. Cereb. Blood Flow Metab. (1997) [Pubmed]
  15. Nicotine exposure during a postnatal critical period alters NR2A and NR2B mRNA expression in rat auditory forebrain. Hsieh, C.Y., Leslie, F.M., Metherate, R. Brain Res. Dev. Brain Res. (2002) [Pubmed]
  16. Neuroprotective effect of ONO-1078, a leukotriene receptor antagonist, on transient global cerebral ischemia in rats. Zhang, L.H., Wei, E.Q. Acta Pharmacol. Sin. (2003) [Pubmed]
  17. The molecular basis of NMDA receptor subtypes: native receptor diversity is predicted by subunit composition. Buller, A.L., Larson, H.C., Schneider, B.E., Beaton, J.A., Morrisett, R.A., Monaghan, D.T. J. Neurosci. (1994) [Pubmed]
  18. Neuronal activity differentially regulates NMDA receptor subunit expression in cerebellar granule cells. Vallano, M.L., Lambolez, B., Audinat, E., Rossier, J. J. Neurosci. (1996) [Pubmed]
  19. CaMKII-dependent phosphorylation regulates SAP97/NR2A interaction. Gardoni, F., Mauceri, D., Fiorentini, C., Bellone, C., Missale, C., Cattabeni, F., Di Luca, M. J. Biol. Chem. (2003) [Pubmed]
  20. H-Ras modulates N-methyl-D-aspartate receptor function via inhibition of Src tyrosine kinase activity. Thornton, C., Yaka, R., Dinh, S., Ron, D. J. Biol. Chem. (2003) [Pubmed]
  21. Molecular characterization of the family of the N-methyl-D-aspartate receptor subunits. Ishii, T., Moriyoshi, K., Sugihara, H., Sakurada, K., Kadotani, H., Yokoi, M., Akazawa, C., Shigemoto, R., Mizuno, N., Masu, M. J. Biol. Chem. (1993) [Pubmed]
  22. N-methyl-D-aspartate receptor subunit changes after traumatic injury to the developing brain. Giza, C.C., Maria, N.S., Hovda, D.A. J. Neurotrauma (2006) [Pubmed]
  23. The NMDA receptor subunits NR2A and NR2B show histological and ultrastructural localization patterns similar to those of NR1. Petralia, R.S., Wang, Y.X., Wenthold, R.J. J. Neurosci. (1994) [Pubmed]
  24. Protein kinase C modulation of recombinant NMDA receptor currents: roles for the C-terminal C1 exon and calcium ions. Logan, S.M., Rivera, F.E., Leonard, J.P. J. Neurosci. (1999) [Pubmed]
  25. Subunit-specific interactions of cyanide with the N-methyl-D-aspartate receptor. Arden, S.R., Sinor, J.D., Potthoff, W.K., Aizenman, E. J. Biol. Chem. (1998) [Pubmed]
  26. NMDA receptor subunits are modified transcriptionally and post-translationally in the brain of streptozotocin-diabetic rats. Di Luca, M., Ruts, L., Gardoni, F., Cattabeni, F., Biessels, G.J., Gispen, W.H. Diabetologia (1999) [Pubmed]
  27. The serine protease plasmin cleaves the amino-terminal domain of the NR2A subunit to relieve zinc inhibition of the N-methyl-D-aspartate receptors. Yuan, H., Vance, K.M., Junge, C.E., Geballe, M.T., Snyder, J.P., Hepler, J.R., Yepes, M., Low, C.M., Traynelis, S.F. J. Biol. Chem. (2009) [Pubmed]
  28. The synaptic localization of NR2B-containing NMDA receptors is controlled by interactions with PDZ proteins and AP-2. Prybylowski, K., Chang, K., Sans, N., Kan, L., Vicini, S., Wenthold, R.J. Neuron (2005) [Pubmed]
  29. Hippocampal synaptic plasticity involves competition between Ca2+/calmodulin-dependent protein kinase II and postsynaptic density 95 for binding to the NR2A subunit of the NMDA receptor. Gardoni, F., Schrama, L.H., Kamal, A., Gispen, W.H., Cattabeni, F., Di Luca, M. J. Neurosci. (2001) [Pubmed]
  30. Immunocytochemical localization of the synapse-associated protein SAP102 in the rat retina. Koulen, P., Garner, C.C., Wässle, H. J. Comp. Neurol. (1998) [Pubmed]
  31. NMDA receptor subunits are phosphorylated by activation of neurotrophin receptors in PSD of rat spinal cord. Di Luca, M., Gardoni, F., Finardi, A., Pagliardini, S., Cattabeni, F., Battaglia, G., Missale, C. Neuroreport (2001) [Pubmed]
  32. Differential expression of N-methyl-D-aspartate receptor subunit messenger ribonucleic acids and immunoreactivity in the rat neostriatum during postnatal development. Lau, W.K., Lui, P.W., Wong, C.K., Chan, Y.S., Yung, K.K. Neurochem. Int. (2003) [Pubmed]
  33. The role of NMDA receptor upregulation in phencyclidine-induced cortical apoptosis in organotypic culture. Wang, C., Fridley, J., Johnson, K.M. Biochem. Pharmacol. (2005) [Pubmed]
  34. N-Methyl-D-aspartate receptor subunit expression in GnRH neurons changes during reproductive senescence in the female rat. Miller, B.H., Gore, A.C. Endocrinology (2002) [Pubmed]
  35. Reduced NR2A expression and prolonged decay of NMDA receptor-mediated synaptic current in rat vagal motoneurons following axotomy. Nabekura, J., Ueno, T., Katsurabayashi, S., Furuta, A., Akaike, N., Okada, M. J. Physiol. (Lond.) (2002) [Pubmed]
  36. Changes in expression of N-methyl-D-aspartate receptor subunits in the rat neostriatum after a single dose of antisense oligonucleotide specific for N-methyl-D-aspartate receptor 1 subunit. Lai, S.K., Wong, C.K., Yang, M.S., Yung, K.K. Neuroscience (2000) [Pubmed]
  37. Synaptic distribution of the NR1, NR2A and NR2B subunits of the N-methyl-d-aspartate receptor in the rat lumbar spinal cord revealed with an antigen-unmasking technique. Nagy, G.G., Watanabe, M., Fukaya, M., Todd, A.J. Eur. J. Neurosci. (2004) [Pubmed]
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