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Grin2b  -  glutamate receptor, ionotropic, NMDA2B...

Mus musculus

Synonyms: AW490526, GluN2B, GluRepsilon2, Glutamate receptor ionotropic, NMDA 2B, N-methyl D-aspartate receptor subtype 2B, ...
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Disease relevance of Grin2b


Psychiatry related information on Grin2b

  • Thalamocortical synaptic plasticity in the mouse is dependent on NMDARs containing the NR2B subunit, which are the dominant form during the "critical period" window for plasticity [4].
  • The NR2B KI mice exhibited normal locomotor activity making this ifenprodil-insensitive mouse model a valuable tool to test the specificity of NR2B selective antagonists in vivo [5].
  • We conclude that the NR2B-selective conantokins may find utility as neuropharmacological tools for probing NMDAR-related mechanisms of opiate dependence [6].
  • Role of NR2B-type NMDA receptors in selective neurodegeneration in Huntington disease [7].
  • Together, these results suggest that Fyn can modulate alcohol consumption and prevent behavioural changes during alcohol withdrawal, possibly via phosphorylation of NR2B [8].

High impact information on Grin2b


Chemical compound and disease context of Grin2b


Biological context of Grin2b


Anatomical context of Grin2b

  • In the hippocampus, the NR2A subunit is believed to be involved in the induction of LTP, whereas the NR2B subunit contributes to the formation of LTD [19].
  • Electron microscopy showed that the phosphorylated NR2B was localized at the postsynaptic density in the spinal cord of mice with neuropathic pain [20].
  • 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 [21].
  • In order to specify the distinct participation of each of these subunits, we focused on the GluRepsilon2 subunits, which are expressed mainly in the forebrain [22].
  • Taking that high levels of GluRepsilon1, GluRepsilon2, and GluRzeta1 subunits are also found in the adult hippocampus and cerebral cortex, it can be assumed that NMDA receptors in developing motoneurons are highly potent and potentially involved in structural and functional development of the brainstem motor system [23].

Associations of Grin2b with chemical compounds

  • Ifenprodil, which interacts with polyamine sites of NR2B-containing NMDA receptors, had no effect [24].
  • As expected, the inhibition of whole cell currents by the NR2B-specific antagonist, ifenprodil, progressively decreased from 69.5 +/- 2.4% [6 days in vitro (DIV)] to 54.9 +/- 2.6% (8 DIV), before reaching a plateau in the second week (42.5 +/- 2%, 12-19 DIV) [25].
  • Concomitant with the NR2B phosphorylation, an increase in neuronal nitric oxide synthase activity was visualized in the superficial dorsal horn of neuropathic pain mice by NADPH diaphorase histochemistry [20].
  • Indomethacin, an inhibitor of prostaglandin (PG) synthesis, and PGE receptor subtype EP1-selective antagonist reduced the NR2B phosphorylation in these mice [20].
  • The N-methyl-D-aspartate (NMDA)-type glutamate receptor GluRepsilon2 is important for delay and trace eyeblink conditioning in mice [22].

Physical interactions of Grin2b

  • In the absence of PSD-93, PSD-95 still interacted with NR2B and nNOS [26].
  • We have previously shown that autophosphorylation of CaMKII induces high-affinity binding to the NR2B subunit of the NMDA receptor (Strack, S., and Colbran, R. J. (1998) J. Biol. Chem. 273, 20689-20692) [27].
  • These results confirm the observations obtained with other basic molecules and suggest that the behavior induced by poly-l-lysine is mediated through the activation of the NMDA receptor ion-channel complex acting either on the polyamine recognition site or on the NR2B subunit [28].

Regulatory relationships of Grin2b


Other interactions of Grin2b

  • Long-term NR2B expression in the cerebellum alters granule cell development and leads to NR2A down-regulation and motor deficits [14].
  • GluRepsilon3 subunit mRNAs were not synthesized by NE-7C2 cells and increased numbers of messages from the GluRepsilon2 gene were detected only after neural network formation [32].
  • In primary striatal cultures, NT-3 treatment induced an enhancement in NR2A, but not NR2B, protein levels [33].
  • Neuropathic pain and NR2B phosphorylation at Tyr1472 were attenuated by the NR2B-selective antagonist CP-101,606 and disappeared in mice lacking Fyn kinase, a Src-family tyrosine kinase [20].
  • Immunoblot analyses from behaviorally symptomatic Mecp2-null mice reveal altered expression of N-methyl-d-aspartate receptor subunits NR2A and NR2B [34].

Analytical, diagnostic and therapeutic context of Grin2b

  • Semi-quantitative RT-PCR studies on striatal tissue in the oldest age group confirmed the significant decrease in NR2A and also showed a decrease in NR2B [35].
  • NR2B protein level was transiently elevated in both trained and stimulated control groups [36].
  • Genetic enhancement of inflammatory pain by forebrain NR2B overexpression [11].
  • Here, we show that residues 1290-1309 in the cytosolic tail of NR2B are critical for CaMKII binding and identify by site-directed mutagenesis several key residues (Lys(1292), Leu(1298), Arg(1299), Arg(1300), Gln(1301), and Ser(1303)) [27].
  • A model is now proposed in which the M2 loop of NR2B is folded in such a way that NR2B(W607) is positioned at the narrow constriction, at a level similar to NR2B(N616) and NR1(N616), with these three residues forming a binding site for Mg2+ [37].


  1. 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]
  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. Role of NMDA receptor subtypes in the induction of catalepsy and increase in Fos protein expression after administration of haloperidol. Yanahashi, S., Hashimoto, K., Hattori, K., Yuasa, S., Iyo, M. Brain Res. (2004) [Pubmed]
  4. 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]
  5. A genetically modified mouse model probing the selective action of ifenprodil at the N-methyl-d-aspartate type 2B receptor. Rosahl, T.W., Wingrove, P.B., Hunt, V., Fradley, R.L., Lawrence, J.M., Heavens, R.P., Treacey, P., Usala, M., Macaulay, A., Bonnert, T.P., Whiting, P.J., Wafford, K.A. Mol. Cell. Neurosci. (2006) [Pubmed]
  6. Conantokins and variants derived from cone snail venom inhibit naloxone-induced withdrawal jumping in morphine-dependent mice. Wei, J., Dong, M., Xiao, C., Jiang, F., Castellino, F.J., Prorok, M., Dai, Q. Neurosci. Lett. (2006) [Pubmed]
  7. Role of NR2B-type NMDA receptors in selective neurodegeneration in Huntington disease. Li, L., Fan, M., Icton, C.D., Chen, N., Leavitt, B.R., Hayden, M.R., Murphy, T.H., Raymond, L.A. Neurobiol. Aging (2003) [Pubmed]
  8. Resistance to alcohol withdrawal-induced behaviour in Fyn transgenic mice and its reversal by ifenprodil. Stork, O., Kojima, N., Stork, S., Kume, N., Obata, K. Brain Res. Mol. Brain Res. (2002) [Pubmed]
  9. Kinesin superfamily motor protein KIF17 and mLin-10 in NMDA receptor-containing vesicle transport. Setou, M., Nakagawa, T., Seog, D.H., Hirokawa, N. Science (2000) [Pubmed]
  10. Regulation of NMDA receptor trafficking by amyloid-beta. Snyder, E.M., Nong, Y., Almeida, C.G., Paul, S., Moran, T., Choi, E.Y., Nairn, A.C., Salter, M.W., Lombroso, P.J., Gouras, G.K., Greengard, P. Nat. Neurosci. (2005) [Pubmed]
  11. Genetic enhancement of inflammatory pain by forebrain NR2B overexpression. Wei, F., Wang, G.D., Kerchner, G.A., Kim, S.J., Xu, H.M., Chen, Z.F., Zhuo, M. Nat. Neurosci. (2001) [Pubmed]
  12. 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]
  13. Ethanol induces long-term facilitation of NR2B-NMDA receptor activity in the dorsal striatum: implications for alcohol drinking behavior. Wang, J., Carnicella, S., Phamluong, K., Jeanblanc, J., Ronesi, J.A., Chaudhri, N., Janak, P.H., Lovinger, D.M., Ron, D. J. Neurosci. (2007) [Pubmed]
  14. 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]
  15. 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]
  16. Molecular and pharmacological characterization of recombinant rat/mice N-methyl-D-aspartate receptor subtypes in the yeast Saccharomyces cerevisiae. Becker, J., Li, Z., Noe, C.R. Eur. J. Biochem. (1998) [Pubmed]
  17. Hippocampal NMDA receptor subunit expression and watermaze learning in estrogen deficient female mice. Boon, W.C., Diepstraten, J., van der Burg, J., Jones, M.E., Simpson, E.R., van den Buuse, M. Brain Res. Mol. Brain Res. (2005) [Pubmed]
  18. Developmental profile of the changing properties of NMDA receptors at cerebellar mossy fiber-granule cell synapses. Cathala, L., Misra, C., Cull-Candy, S. J. Neurosci. (2000) [Pubmed]
  19. Roles of NMDA receptor NR2A and NR2B subtypes for long-term depression in the anterior cingulate cortex. Toyoda, H., Zhao, M.G., Zhuo, M. Eur. J. Neurosci. (2005) [Pubmed]
  20. 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]
  21. 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]
  22. The N-methyl-D-aspartate (NMDA)-type glutamate receptor GluRepsilon2 is important for delay and trace eyeblink conditioning in mice. Takehara, K., Kawahara, S., Munemoto, Y., Kuriyama, H., Mori, H., Mishina, M., Kirino, Y. Neurosci. Lett. (2004) [Pubmed]
  23. Early onset of NMDA receptor GluR epsilon 1 (NR2A) expression and its abundant postsynaptic localization in developing motoneurons of the mouse hypoglossal nucleus. Oshima, S., Fukaya, M., Masabumi, N., Shirakawa, T., Oguchi, H., Watanabe, M. Neurosci. Res. (2002) [Pubmed]
  24. N-methyl-D-aspartate receptor antagonists enhance histamine neuron activity in rodent brain. Faucard, R., Armand, V., Héron, A., Cochois, V., Schwartz, J.C., Arrang, J.M. J. Neurochem. (2006) [Pubmed]
  25. Synaptic and extrasynaptic NMDA receptor NR2 subunits in cultured hippocampal neurons. Thomas, C.G., Miller, A.J., Westbrook, G.L. J. Neurophysiol. (2006) [Pubmed]
  26. Neonatal hypoxia-ischemia differentially upregulates MAGUKs and associated proteins in PSD-93-deficient mouse brain. Jiang, X., Mu, D., Sheldon, R.A., Glidden, D.V., Ferriero, D.M. Stroke (2003) [Pubmed]
  27. Mechanism and regulation of calcium/calmodulin-dependent protein kinase II targeting to the NR2B subunit of the N-methyl-D-aspartate receptor. Strack, S., McNeill, R.B., Colbran, R.J. J. Biol. Chem. (2000) [Pubmed]
  28. Nociceptive behavior induced by poly-L-lysine and other basic compounds involves the spinal NMDA receptors. Tan-No, K., Esashi, A., Nakagawasai, O., Niijima, F., Sakurada, C., Sakurada, T., Bakalkin, G., Terenius, L., Tadano, T. Brain Res. (2004) [Pubmed]
  29. Fyn is required for haloperidol-induced catalepsy in mice. Hattori, K., Uchino, S., Isosaka, T., Maekawa, M., Iyo, M., Sato, T., Kohsaka, S., Yagi, T., Yuasa, S. J. Biol. Chem. (2006) [Pubmed]
  30. 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]
  31. Differential modulation of Ca2+/calmodulin-dependent protein kinase II activity by regulated interactions with N-methyl-D-aspartate receptor NR2B subunits and alpha-actinin. Robison, A.J., Bartlett, R.K., Bass, M.A., Colbran, R.J. J. Biol. Chem. (2005) [Pubmed]
  32. 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]
  33. Mice heterozygous for neurotrophin-3 display enhanced vulnerability to excitotoxicity in the striatum through increased expression of N-methyl-d-aspartate receptors. Torres-Peraza, J., Pezzi, S., Canals, J.M., Gavald??, N., Garc??a-Mart??nez, J.M., P??rez-Navarro, E., Alberch, J. Neuroscience (2007) [Pubmed]
  34. Hippocampal synaptic plasticity is impaired in the Mecp2-null mouse model of Rett syndrome. Asaka, Y., Jugloff, D.G., Zhang, L., Eubanks, J.H., Fitzsimonds, R.M. Neurobiol. Dis. (2006) [Pubmed]
  35. Changes in Expression of N-Methyl-D-Aspartate Receptor Subunits Occur Early in the R6/2 Mouse Model of Huntington's Disease. Ali, N.J., Levine, M.S. Dev. Neurosci. (2006) [Pubmed]
  36. Differential regulation of cortical NMDA receptor subunits by sensory learning. Skibinska, A., Lech, M., Kossut, M. Brain Res. (2005) [Pubmed]
  37. The selectivity filter of the N-methyl-D-aspartate receptor: a tryptophan residue controls block and permeation of Mg2+. Williams, K., Pahk, A.J., Kashiwagi, K., Masuko, T., Nguyen, N.D., Igarashi, K. Mol. Pharmacol. (1998) [Pubmed]
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