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Grin2a  -  glutamate receptor, ionotropic, NMDA2A...

Mus musculus

Synonyms: GluN2A, GluRepsilon1, Glutamate receptor ionotropic, NMDA 2A, N-methyl D-aspartate receptor subtype 2A, NMDAR2A, ...
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Disease relevance of Grin2a


Psychiatry related information on Grin2a


High impact information on Grin2a

  • In particular, it has been suggested that NR2A-containing NMDA receptors are involved in LTP induction, whereas NR2B-containing receptors are involved in LTD induction in the hippocampus [8].
  • Here we report that the activation of the NR2B and NR2A subunits of the NMDA receptor is critical for the induction of cingulate LTP, regardless of the induction protocol [8].
  • Lu and colleagues (Lu et al., 2001 [this issue of Neuron]) now report that mice lacking the NR2A subunit display normal duration of critical periods of barrel cortex plasticity [9].
  • We hypothesize that NR2A-rich NMDARs may be localized to the center of developing synapses by an activity-dependent process that involves the targeting of PSD-95 to the postsynaptic density [10].
  • Developmental loss of miniature N-methyl-D-aspartate receptor currents in NR2A knockout mice [10].

Biological context of Grin2a

  • The comparison of NR1a-NR2A and NR1a-NR2B receptors shows that the voltage-dependent inhibition is similar in both types of receptors but that the voltage-independent inhibition occurs at much lower Zn2+ concentrations in NR1a-NR2A receptors (IC50 in the nanomolar range) than in NR1a-NR2B receptors (IC50 in the micromolar range) [11].
  • The high affinity of the effect observed with NR1a-NR2A receptors was found to be attributable mostly to the slow dissociation of Zn2+ from its binding site [11].
  • Increased NR2B subunit levels led also to a gradual down-regulation of cerebellar NR2A levels, preceding the development of motor impairment in adult animals [12].
  • In a human embryonic kidney (HEK) 293 cell expression system, PTPalpha enhanced fyn-mediated NR2A and NR2B tyrosine phosphorylation by several-fold [13].
  • Here, we used hind paw injection of formalin, complete Freund's adjuvant and a nerve injury model to investigate the effects of GluRepsilon 1 subunit gene deletion on pain-related behavior in mice [14].

Anatomical context of Grin2a

  • The GluRepsilon1 subunit knockout also reduced NMDA EPSCs at the C/A-CA3 synapses on basal dendrites, but did not affect NMDA EPSCs at the commissural-CA3 synapses on basal dendrites [15].
  • These results confirmed our previous findings that NMDA receptors operating at different synapses in CA3 pyramidal cells have different GluRepsilon subunit compositions, and further show that the GluRepsilon subunit composition may be regulated depending on the types of synaptic inputs, even within a single CA3 pyramidal neuron [15].
  • Wild-type, NR2A-deficient, and NR2D-deficient mice developed neuropathic pain; in addition, phosphorylation of NR2B subunits of NMDA receptors at Tyr1472 was observed in the superficial dorsal horn of the spinal cord 1 week after nerve injury [16].
  • As Purkinje cells are exceptionally lacking GluRepsilon expression, the discrepant result may provide in vivo evidence suggesting the importance of accompanying GluRepsilon subunits in synaptic localization of GluRzeta1 [17].
  • NR1 and NR2A subunit proteins were detected both in nondifferentiated progenitor cells and in neurons, while the mature form of NR2B subunit protein appeared only at the time of neuronal process elongation [18].

Associations of Grin2a with chemical compounds

  • Chelation of a contaminant metal also could account for the rapid NR2A subunit-specific potentiations produced by reducing compounds like DTT or glutathione [11].
  • CONCLUSIONS: Results suggest that the loss of NR2A subunit-containing NMDA receptors impairs the ability to form or express learned reward-related responses to ethanol and causes deficits in motor coordination [19].
  • OBJECTIVES: In the current study, we assessed the relative roles of NMDA subunits via phenotypic assessment of ethanol-related behaviors in NR2A knockout (KO) mice [19].
  • However, glutamate-evoked NMDA receptor currents were reduced by the GluRepsilon1 subunit knockout to a similar extent at both apical and basal dendrites [15].
  • While wild-type, GluRepsilon1(-/-), GluRepsilon4(-/-), and GluRepsilon1(-/-)/epsilon4(-/-) mice all died by ammonium chloride at 12 mmol/kg during the first tonic convulsions, two of eight GluRepsilon3(-/-) mice survived [20].

Physical interactions of Grin2a

  • Immunoblot analyses revealed that the predominantly tyrosine-phosphorylated proteins in the NMDA receptor complex are the NR2A/B subunits and a novel 120 kDa protein [21].

Regulatory relationships of Grin2a

  • 4. Absence of BDNF induced a reduction of NR2A level [22].
  • Their inhibitors blocked NR2A induction and phosphorylation as well as neuronal death induced by NT-4/5 [23].
  • Evidence suggests that, in the CA1 region of the hippocampus, NR2A-containing NMDARs promote LTP whereas NR2B-containing receptors promote LTD [24].

Other interactions of Grin2a

  • Long-term NR2B expression in the cerebellum alters granule cell development and leads to NR2A down-regulation and motor deficits [12].
  • RT-PCR studies revealed that GluRepsilon1 and GluRepsilon4 subunit mRNAs were transcribed by both non-induced and neuronally differentiated cells [25].
  • RATIONALE: The ionotropic NMDA glutamate receptor is composed of NR1 and NR2 (NR2A-D) subunits [19].
  • Consistent with the known functional localization, GluRepsilon1, GluRepsilon3, and GluRzeta1 are, thus, anatomically concentrated at the mossy fibre-granule cell synapse [17].
  • Double immunofluorescence with the AMPA receptor GluRalpha1 (GluR1 or GluR-A) subunit further demonstrated that the GluRepsilon1 subunit was colocalized in a subset, not all, of GluRalpha1-immunopositive structures in the stratum lucidum [26].

Analytical, diagnostic and therapeutic context of Grin2a

  • In the present study, we employed a mouse gene-targeting approach to examine the role of the NR2A subunit in the mediation of anxiety- and depressive-related behaviors [6].
  • NR2A KO mice showed antidepressant-like profiles in the forced swim test and tail suspension test, as compared to WT controls [6].
  • In addition, our findings suggest that GluRepsilon1 mutant mice are useful as an animal model of psychosis that is associated with NMDA receptor malfunction and hyperfunction of dopaminergic and serotonergic neuronal systems [27].
  • Western blots revealed the induction of NR2A by NT-4/5 [23].
  • Immunocytochemistry revealed that dendrites and somas displayed distinct NR1 and NR2A subunit clusters which became increasingly colocalized in +/+ neurones [28].


  1. Attenuation of focal ischemic brain injury in mice deficient in the epsilon1 (NR2A) subunit of NMDA receptor. Morikawa, E., Mori, H., Kiyama, Y., Mishina, M., Asano, T., Kirino, T. J. Neurosci. (1998) [Pubmed]
  2. Immunity and behavior: antibodies alter emotion. Huerta, P.T., Kowal, C., DeGiorgio, L.A., Volpe, B.T., Diamond, B. Proc. Natl. Acad. Sci. U.S.A. (2006) [Pubmed]
  3. Characterization of N-methyl-D-aspartate receptor subunits responsible for postoperative pain. Nishimura, W., Muratani, T., Tatsumi, S., Sakimura, K., Mishina, M., Minami, T., Ito, S. Eur. J. Pharmacol. (2004) [Pubmed]
  4. Roles of diverse glutamate receptors in brain functions elucidated by subunit-specific and region-specific gene targeting. Mori, H., Mishina, M. Life Sci. (2003) [Pubmed]
  5. Barrel cortex critical period plasticity is independent of changes in NMDA receptor subunit composition. Lu, H.C., Gonzalez, E., Crair, M.C. Neuron (2001) [Pubmed]
  6. Genetic Inactivation of the NMDA Receptor NR2A Subunit has Anxiolytic- and Antidepressant-Like Effects in Mice. Boyce-Rustay, J.M., Holmes, A. Neuropsychopharmacology (2006) [Pubmed]
  7. Behavioural adaptations to addictive drugs in mice lacking the NMDA receptor epsilon1 subunit. Miyamoto, Y., Yamada, K., Nagai, T., Mori, H., Mishina, M., Furukawa, H., Noda, Y., Nabeshima, T. Eur. J. Neurosci. (2004) [Pubmed]
  8. Roles of NMDA NR2B subtype receptor in prefrontal long-term potentiation and contextual fear memory. Zhao, M.G., Toyoda, H., Lee, Y.S., Wu, L.J., Ko, S.W., Zhang, X.H., Jia, Y., Shum, F., Xu, H., Li, B.M., Kaang, B.K., Zhuo, M. Neuron (2005) [Pubmed]
  9. Do NMDA receptor kinetics regulate the end of critical periods of plasticity? Medina, A.E., Liao, D.S., Mower, A.F., Ramoa, A.S. Neuron (2001) [Pubmed]
  10. Developmental loss of miniature N-methyl-D-aspartate receptor currents in NR2A knockout mice. Townsend, M., Yoshii, A., Mishina, M., Constantine-Paton, M. Proc. Natl. Acad. Sci. U.S.A. (2003) [Pubmed]
  11. High-affinity zinc inhibition of NMDA NR1-NR2A receptors. Paoletti, P., Ascher, P., Neyton, J. J. Neurosci. (1997) [Pubmed]
  12. Long-term NR2B expression in the cerebellum alters granule cell development and leads to NR2A down-regulation and motor deficits. Schlett, K., Pieri, I., Metzger, F., Marchetti, L., Steigerwald, F., Dere, E., Kirilly, D., Tárnok, K., Barabás, B., Varga, A.K., Gerspach, J., Huston, J., Pfizenmaier, K., Köhr, G., Eisel, U.L. Mol. Cell. Neurosci. (2004) [Pubmed]
  13. Reduced NMDA receptor tyrosine phosphorylation in PTPalpha-deficient mouse synaptosomes is accompanied by inhibition of four src family kinases and Pyk2: an upstream role for PTPalpha in NMDA receptor regulation. Le, H.T., Maksumova, L., Wang, J., Pallen, C.J. J. Neurochem. (2006) [Pubmed]
  14. Unaltered pain-related behavior in mice lacking NMDA receptor GluRepsilon 1 subunit. Petrenko, A.B., Yamakura, T., Baba, H., Sakimura, K. Neurosci. Res. (2003) [Pubmed]
  15. Input-specific targeting of NMDA receptor subtypes at mouse hippocampal CA3 pyramidal neuron synapses. Ito, I., Kawakami, R., Sakimura, K., Mishina, M., Sugiyama, H. Neuropharmacology (2000) [Pubmed]
  16. Fyn kinase-mediated phosphorylation of NMDA receptor NR2B subunit at Tyr1472 is essential for maintenance of neuropathic pain. Abe, T., Matsumura, S., Katano, T., Mabuchi, T., Takagi, K., Xu, L., Yamamoto, A., Hattori, K., Yagi, T., Watanabe, M., Nakazawa, T., Yamamoto, T., Mishina, M., Nakai, Y., Ito, S. Eur. J. Neurosci. (2005) [Pubmed]
  17. NMDA receptor subunits GluRepsilon1, GluRepsilon3 and GluRzeta1 are enriched at the mossy fibre-granule cell synapse in the adult mouse cerebellum. Yamada, K., Fukaya, M., Shimizu, H., Sakimura, K., Watanabe, M. Eur. J. Neurosci. (2001) [Pubmed]
  18. Regulated appearance of NMDA receptor subunits and channel functions during in vitro neuronal differentiation. Jelitai, M., Schlett, K., Varju, P., Eisel, U., Madarász, E. J. Neurobiol. (2002) [Pubmed]
  19. Ethanol-related behaviors in mice lacking the NMDA receptor NR2A subunit. Boyce-Rustay, J.M., Holmes, A. Psychopharmacology (Berl.) (2006) [Pubmed]
  20. Characterization of N-methyl-D-aspartate receptor subunits involved in acute ammonia toxicity. Kitano, T., Matsumura, S., Seki, T., Hikida, T., Sakimura, K., Nagano, T., Mishina, M., Nakanishi, S., Ito, S. Neurochem. Int. (2004) [Pubmed]
  21. Identification of PSD-93 as a substrate for the Src family tyrosine kinase Fyn. Nada, S., Shima, T., Yanai, H., Husi, H., Grant, S.G., Okada, M., Akiyama, T. J. Biol. Chem. (2003) [Pubmed]
  22. NR2A but not NR2B N-methyl-D-aspartate receptor subunit is altered in the visual cortex of BDNF-knock-out mice. Margottil, E., Domenici, L. Cell. Mol. Neurobiol. (2003) [Pubmed]
  23. NR2A induction and NMDA receptor-dependent neuronal death by neurotrophin-4/5 in cortical cell culture. Choi, S.Y., Hwang, J.J., Koh, J.Y. J. Neurochem. (2004) [Pubmed]
  24. Distinct roles for Ras-guanine nucleotide-releasing factor 1 (Ras-GRF1) and Ras-GRF2 in the induction of long-term potentiation and long-term depression. Li, S., Tian, X., Hartley, D.M., Feig, L.A. J. Neurosci. (2006) [Pubmed]
  25. Schedule of NMDA receptor subunit expression and functional channel formation in the course of in vitro-induced neurogenesis. Varju, P., Schlett, K., Eisel, U., Madarász, E. J. Neurochem. (2001) [Pubmed]
  26. Selective scarcity of NMDA receptor channel subunits in the stratum lucidum (mossy fibre-recipient layer) of the mouse hippocampal CA3 subfield. Watanabe, M., Fukaya, M., Sakimura, K., Manabe, T., Mishina, M., Inoue, Y. Eur. J. Neurosci. (1998) [Pubmed]
  27. Hyperfunction of dopaminergic and serotonergic neuronal systems in mice lacking the NMDA receptor epsilon1 subunit. Miyamoto, Y., Yamada, K., Noda, Y., Mori, H., Mishina, M., Nabeshima, T. J. Neurosci. (2001) [Pubmed]
  28. Deletion of the NR2A subunit prevents developmental changes of NMDA-mEPSCs in cultured mouse cerebellar granule neurones. Fu, Z., Logan, S.M., Vicini, S. J. Physiol. (Lond.) (2005) [Pubmed]
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