Gene Symbol: GRIN2C
Description: glutamate ionotropic receptor NMDA type subunit 2C
Alias: GluN2C, NMDAR2C, NR2C, glutamate receptor ionotropic, NMDA 2C, N-methyl D-aspartate receptor subtype 2C, N-methyl-D-aspartate receptor subunit 2C, glutamate [NMDA] receptor subunit epsilon-3, glutamate receptor, ionotropic, N-methyl D-aspartate 2C
Species: human
Products:     GRIN2C

Top Publications

  1. Monyer H, Sprengel R, Schoepfer R, Herb A, Higuchi M, Lomeli H, et al. Heteromeric NMDA receptors: molecular and functional distinction of subtypes. Science. 1992;256:1217-21 pubmed
    ..identified three complementary DNA species of rat brain, encoding NMDA receptor subunits NMDAR2A (NR2A), NR2B, and NR2C, which are 55 to 70% identical in sequence...
  2. Kornau H, Schenker L, Kennedy M, Seeburg P. Domain interaction between NMDA receptor subunits and the postsynaptic density protein PSD-95. Science. 1995;269:1737-40 pubmed
    ..The interaction of these proteins may affect the plasticity of excitatory synapses. ..
  3. Haughey N, Nath A, Mattson M, Slevin J, Geiger J. HIV-1 Tat through phosphorylation of NMDA receptors potentiates glutamate excitotoxicity. J Neurochem. 2001;78:457-67 pubmed
    ..Together, these findings suggest that NMDA receptors play an important role in Tat neurotoxicity and the mechanisms identified may provide additional therapeutic targets for the treatment of HIV-1 associated dementia. ..
  4. Williams N, Bowen T, Spurlock G, Norton N, Williams H, Hoogendoorn B, et al. Determination of the genomic structure and mutation screening in schizophrenic individuals for five subunits of the N-methyl-D-aspartate glutamate receptor. Mol Psychiatry. 2002;7:508-14 pubmed
    ..2). These SNPs will therefore be suitable for studying neuropsychiatric phenotypes that are putatively related to NMDA dysfunction. Pooled analysis provided no support for association between any of the GRIN genes and schizophrenia. ..
  5. Eugenin E, King J, Nath A, Calderon T, Zukin R, Bennett M, et al. HIV-tat induces formation of an LRP-PSD-95- NMDAR-nNOS complex that promotes apoptosis in neurons and astrocytes. Proc Natl Acad Sci U S A. 2007;104:3438-43 pubmed
    ..These findings implicate the complex in HIV-induced neuronal apoptosis and suggest therapeutic targets for intervention in the pathogenesis of NeuroAIDS. ..
  6. Mullasseril P, Hansen K, Vance K, Ogden K, Yuan H, Kurtkaya N, et al. A subunit-selective potentiator of NR2C- and NR2D-containing NMDA receptors. Nat Commun. 2010;1:90 pubmed publisher
    ..In this article, we identify a novel subunit-selective potentiator of NMDA receptors containing the NR2C or NR2D subunit, which could allow selective modification of circuit function in regions expressing NR2C/D subunits...
  7. Shin A, Thayer S. Human immunodeficiency virus-1 protein Tat induces excitotoxic loss of presynaptic terminals in hippocampal cultures. Mol Cell Neurosci. 2013;54:22-9 pubmed publisher
    ..Understanding the dynamics of synaptic changes in response to HIV infection of the CNS may lead to the design of improved pharmacotherapies for HAND patients. ..
  8. Pittaluga A, Pattarini R, Severi P, Raiteri M. Human brain N-methyl-D-aspartate receptors regulating noradrenaline release are positively modulated by HIV-1 coat protein gp120. AIDS. 1996;10:463-8 pubmed 120 binds directly through the V3 loop at noradrenergic axon terminals in human brain neocortex and may alter the function of presynaptic NMDA receptors mediating regulation of noradrenaline release. ..
  9. Akesson E, Kjaeldgaard A, Samuelsson E, Seiger A, Sundstrom E. Ionotropic glutamate receptor expression in human spinal cord during first trimester development. Brain Res Dev Brain Res. 2000;119:55-63 pubmed
    ..5 weeks of gestation. Immunoreactive bands corresponding to the NMDA receptor subunits NR1, NR2A, NR2B, NR2C and NR2D were demonstrated by immunoblotting at the earliest between 4...

More Information

Publications106 found, 100 shown here

  1. Merrick B, Auerbach S, Stockton P, Foley J, Malarkey D, Sills R, et al. Testing an aflatoxin B1 gene signature in rat archival tissues. Chem Res Toxicol. 2012;25:1132-44 pubmed publisher
    ..The 14 genes evaluated were Adam8, Cdh13, Ddit4l, Mybl2, Akr7a3, Akr7a2, Fhit, Wwox, Abcb1b, Abcc3, Cxcl1, Gsta5, Grin2c, and the C8orf46 homologue...
  2. Manzardo A, McGuire A, Butler M. Clinically relevant genetic biomarkers from the brain in alcoholism with representation on high resolution chromosome ideograms. Gene. 2015;560:184-94 pubmed publisher
    ..HTR3A, HTR1B, HTR3B, and SLC6A4), GABAergic (e.g., GABRA1, GABRA2, and GABRG1), glutaminergic (GAD1, GRIK3, and GRIN2C) and opioid (e.g., OPRM1, OPRD1, and OPRK1) pathways which presumably impact reinforcing properties of alcohol...
  3. Menezes F, Kist L, Bogo M, Bonan C, da Silva R. Evaluation of age-dependent response to NMDA receptor antagonism in zebrafish. Zebrafish. 2015;12:137-43 pubmed publisher
    ..1 had a slight reduction throughout the development, while the NR2 subunits, especially NR2A.2 and NR2C.1, vary their expression levels according to the stage of development...
  4. Kim N, Choi Y, Lim S, Jeong M, Jin D, Choi C. Effect of salinity changes on olfactory memory-related genes and hormones in adult chum salmon Oncorhynchus keta. Comp Biochem Physiol A Mol Integr Physiol. 2015;187:40-7 pubmed publisher
    ..We examined changes in the expression of three NRs (NR1, NR2B, and NR2C), olfactory receptor (OR), and adrenocorticotropic hormone (ACTH) in chum salmon Oncorhynchus keta using ..
  5. Hillman B, Gupta S, Stairs D, Buonanno A, Dravid S. Behavioral analysis of NR2C knockout mouse reveals deficit in acquisition of conditioned fear and working memory. Neurobiol Learn Mem. 2011;95:404-14 pubmed publisher
    ..The precise role of NR2C-containing receptors in vivo is poorly understood...
  6. Marzec P, Armenise C, Pérot G, Roumelioti F, Basyuk E, Gagos S, et al. Nuclear-receptor-mediated telomere insertion leads to genome instability in ALT cancers. Cell. 2015;160:913-927 pubmed publisher
    ..telomeric DNA is added to multiple discrete sites throughout the genome, corresponding to regions regulated by NR2C/F transcription factors. These proteins drive local telomere DNA addition by recruiting telomeric chromatin...
  7. Liu H, Peng L, So J, Tsang K, Chong C, Mak P, et al. TSPYL2 Regulates the Expression of EZH2 Target Genes in Neurons. Mol Neurobiol. 2019;56:2640-2652 pubmed publisher
    ..significantly reduced expression of genes including Gbx2 and Prss16 from cluster 1 and Acvrl1, Bdnf, Egr3, Grin2c, and Igf1 from cluster 2 in the mutant...
  8. Bach P, Kirsch M, Hoffmann S, Jorde A, Mann K, Frank J, et al. The effects of single nucleotide polymorphisms in glutamatergic neurotransmission genes on neural response to alcohol cues and craving. Addict Biol. 2015;20:1022-32 pubmed publisher
    ..of four single nucleotide polymorphisms (SNPs) in the genes of the N-Methyl-d-aspartate receptor (GRIN1, GRIN2A, GRIN2C) and kainate receptor (GRIK1), which have been previously associated with alcoholism, on behavior, neural cue-..
  9. Roshanravan H, Kim E, Dryer S. NMDA Receptors as Potential Therapeutic Targets in Diabetic Nephropathy: Increased Renal NMDA Receptor Subunit Expression in Akita Mice and Reduced Nephropathy Following Sustained Treatment With Memantine or MK-801. Diabetes. 2016;65:3139-50 pubmed publisher
    ..A similar increase in NMDA subunits, especially NR1, NR2A, and NR2C, was observed in glomeruli and tubules of Akita mice...
  10. Jahn A, Rane G, Paszkowski Rogacz M, Sayols S, Bluhm A, Han C, et al. ZBTB48 is both a vertebrate telomere-binding protein and a transcriptional activator. EMBO Rep. 2017;18:929-946 pubmed publisher
    ..interactions are mediated by the CST complex and HOT1/HMBOX1, while subtelomeric variant repeats are recognized by NR2C/F transcription factors...
  11. Blanco E, Pavón F, Palomino A, Luque Rojas M, Serrano A, Rivera P, et al. Cocaine-induced behavioral sensitization is associated with changes in the expression of endocannabinoid and glutamatergic signaling systems in the mouse prefrontal cortex. Int J Neuropsychopharmacol. 2014;18: pubmed publisher
    ..metabotropic glutamate receptors (mGluR3 and GluR), and subunits of NMDA ionotropic receptors (NR1, NR2A, NR2B and NR2C) after acute cocaine administration, while mice repeatedly exposed to cocaine only displayed an increase in NR2C...
  12. Wijayatunge R, Liu F, Shpargel K, Wayne N, Chan U, Boua J, et al. The histone demethylase Kdm6b regulates a mature gene expression program in differentiating cerebellar granule neurons. Mol Cell Neurosci. 2018;87:4-17 pubmed publisher
    ..Loss of Kdm6b also impaired the ability of Brain-Derived Neurotrophic Factor (BDNF) to induce expression of Grin2c and Tiam1 in maturing CGNs...
  13. Chen P, Song J, Luo L, Cheng Q, Xiao H, Gong S. Gene expression of NMDA and AMPA receptors in different facial motor neurons. Laryngoscope. 2016;126:E6-11 pubmed publisher
    ..Messenger RNA (mRNA) of AMPAR subunits (GluR1, GluR2, GluR3, and GluR4) and NMDAR subunits (NR1, NR2a, NR2b, NR2c, and NR2d) was detected in reinnervating and dormant neurons...
  14. Lee L, Cho Y, Lin P, Yeh T, Chang C, Yeh T. Influence of Genetic Variants of the N-Methyl-D-Aspartate Receptor on Emotion and Social Behavior in Adolescents. Neural Plast. 2016;2016:6851592 pubmed publisher
    ..e., GRIN1, GRIN2A, GRIN2B, GRIN2C, and GRIN2D) with emotion and social behavior in adolescents...
  15. Forero D, Herteleer L, De Zutter S, Norrback K, Nilsson L, Adolfsson R, et al. A network of synaptic genes associated with schizophrenia and bipolar disorder. Schizophr Res. 2016;172:68-74 pubmed publisher
    ..genes involved in the cAMP/PKA/CREB functional pathway that could be novel candidates for BP and SZ: CREB1, CREM, GRIN2C, NPY2R, NF1, PPP3CB and PRKAR1A...
  16. Wu P, Price P, Du B, Hatch W, Terwilliger E. Direct cytotoxicity of HIV-1 envelope protein gp120 on human NT neurons. Neuroreport. 1996;7:1045-9 pubmed
    ..Taken together, these data indicate that gp120 exerts a direct neurotoxic effect by acting through NMDA receptors and Ca2+ channels. ..
  17. Yu Y, Lin Y, Takasaki Y, Wang C, Kimura H, Xing J, et al. Rare loss of function mutations in N-methyl-D-aspartate glutamate receptors and their contributions to schizophrenia susceptibility. Transl Psychiatry. 2018;8:12 pubmed publisher
    ..We performed a screening study for exonic regions of GRIN1, GRIN2A, GRIN2C, GRIN2D, GRIN3A, and GRIN3B, which encode NMDAR subunits, in 562 participates (370 SCZ and 192 ASD)...
  18. Wang H, Dávila García M, Yarl W, Gondré Lewis M. Gestational nicotine exposure regulates expression of AMPA and NMDA receptors and their signaling apparatus in developing and adult rat hippocampus. Neuroscience. 2011;188:168-81 pubmed publisher
    ..b>NR2c was not detectable...
  19. Takano H, Onodera O, Tanaka H, Mori H, Sakimura K, Hori T, et al. Chromosomal localization of the epsilon 1, epsilon 3 and zeta 1 subunit genes of the human NMDA receptor channel. Biochem Biophys Res Commun. 1993;197:922-6 pubmed
    ..By the fluorescence in situ hybridization, we mapped the genes for the epsilon 1, epsilon 3 and zeta 1 subunits of the human NMDA receptor channel to chromosomes 16p13, 17q25 and 9q34, respectively. ..
  20. Song L, Nath A, Geiger J, Moore A, Hochman S. Human immunodeficiency virus type 1 Tat protein directly activates neuronal N-methyl-D-aspartate receptors at an allosteric zinc-sensitive site. J Neurovirol. 2003;9:399-403 pubmed
    ..Thus, Tat appears to excite neurons via direct activation of the NMDA receptor at an allosteric Zn(2+)-sensitive site. ..
  21. Kim H, Shin A, Thayer S. Activation of cannabinoid type 2 receptors inhibits HIV-1 envelope glycoprotein gp120-induced synapse loss. Mol Pharmacol. 2011;80:357-66 pubmed publisher
    ..These results indicate that cannabinoids prevent the impairment of network function produced by gp120 and, thus, might have therapeutic potential in HAD. ..
  22. Tarabeux J, Kebir O, Gauthier J, Hamdan F, Xiong L, Piton A, et al. Rare mutations in N-methyl-D-aspartate glutamate receptors in autism spectrum disorders and schizophrenia. Transl Psychiatry. 2011;1:e55 pubmed publisher
    ..Truncating mutations in GRIN2C, GRIN3A and GRIN3B were identified in both subjects and controls, but no truncating mutations were found in the ..
  23. Minaya D, Larson R, Podlasz P, Czaja K. Glutamate-dependent regulation of food intake is altered with age through changes in NMDA receptor phenotypes on vagal afferent neurons. Physiol Behav. 2018;189:26-31 pubmed publisher
    ..Immunofluorescence was used to determine NMDA receptor subunit expression (NR1, NR2B, NR2C, and NR2D) in the NG...
  24. Wu H, Hsu F, Gleichman A, Baconguis I, Coulter D, Lynch D. Fyn-mediated phosphorylation of NR2B Tyr-1336 controls calpain-mediated NR2B cleavage in neurons and heterologous systems. J Biol Chem. 2007;282:20075-87 pubmed
    ..Thus, the Fyn-controlled regulation of NMDA receptor cleavage by calpain may play critical roles in controlling NMDA receptor properties during synaptic plasticity and excitotoxicity. ..
  25. Subramanian M, Holt A, Mueller P. Physical activity correlates with glutamate receptor gene expression in spinally-projecting RVLM neurons: a laser capture microdissection study. Brain Res. 2014;1585:51-62 pubmed publisher
    ..There were no significant difference in the gene expression of NMDA (NR1, NR2A, NR2B, NR2C and NR2D), AMPA (GLUR1, GLUR2 and GLUR3) and GABAA (GABAA1 and GABAA2) receptor subunits...
  26. Qi Y, Yang Y. Hunger States Control the Directions of Synaptic Plasticity via Switching Cell Type-Specific Subunits of NMDA Receptors. J Neurosci. 2015;35:13171-82 pubmed publisher
    ..Mechanistically, we also find that food deprivation increases the expressions of NR2C/NR2D/NR3-containing NMDA receptors (NMDARs) at AgRP neurons that contribute to the inductions of LTD, whereas it ..
  27. Aksenov M, Aksenova M, MacTutus C, Booze R. D1/NMDA receptors and concurrent methamphetamine+ HIV-1 Tat neurotoxicity. J Neuroimmune Pharmacol. 2012;7:599-608 pubmed publisher
    ..Overall, our results support the hypothesis that METH and HIV-1 Tat disrupt the normal conjunction of signaling between D1 and NMDA receptors, resulting in neural dysfunction and death. ..
  28. Morhenn V, Nelson T, Gruol D. The rate of wound healing is increased in psoriasis. J Dermatol Sci. 2013;72:87-92 pubmed publisher
    ..Involved and uninvolved skin of individuals with psoriasis shows significantly more rapid healing than normal. The NR2C subunit of NMDAR is down-regulated in the basal cell layer of involved and uninvolved epidermis of psoriatic ..
  29. Oikonomou K, Singh M, Rich M, Short S, Antic S. Contribution of extrasynaptic N-methyl-D-aspartate and adenosine A1 receptors in the generation of dendritic glutamate-mediated plateau potentials. Philos Trans R Soc Lond B Biol Sci. 2015;370: pubmed publisher
    ..We used calcium imaging to study the role of NR2C/D-containing N-methyl-d-aspartate (NMDA) receptors and adenosine A1 receptors in the generation of dendritic NMDA ..
  30. Shang Y, Zhang J, Huang E. HIPK2-Mediated Transcriptional Control of NMDA Receptor Subunit Expression Regulates Neuronal Survival and Cell Death. J Neurosci. 2018;38:4006-4019 pubmed publisher
    ..we showed that the HIPK2-JNK-c-Jun pathway is important in suppressing the transcription of Grin2a and Grin2c, which encodes the GluN2A and GluN2C subunits of the NMDA receptors, respectively...
  31. Chen Y, Lee M, Fang H, Yang J, Chen Y, Tsai H. Paeoniflorin inhibits excitatory amino acid agonist-and high-dose morphine-induced nociceptive behavior in mice via modulation of N-methyl-D-aspartate receptors. BMC Complement Altern Med. 2016;16:240 pubmed publisher
    ..Docking energy data revealed that paeoniflorin had stronger binding activity in NR2A and NR2B than NR2C of NMDA receptors...
  32. Wang P, Barks J, Silverstein F. Tat, a human immunodeficiency virus-1-derived protein, augments excitotoxic hippocampal injury in neonatal rats. Neuroscience. 1999;88:585-97 pubmed
    ..These data support the hypothesis that locally released Tat could exert neurotoxic effects, mediated by N-methyl-D-aspartate receptor activation, in vivo in the immature brain. ..
  33. Rumbaugh J, Bachani M, Li W, Butler T, Smith K, Bianchet M, et al. HIV immune complexes prevent excitotoxicity by interaction with NMDA receptors. Neurobiol Dis. 2013;49:169-76 pubmed publisher
    ..These observations provide rationale for development of vaccine therapies targeting Tat for prevention of HAND. ..
  34. Morhenn V, Nahm W, Mansbridge J. Psoriatic keratinocytes are resistant to tumor necrosis factor alpha's induction of mRNA for the NMDA-R2C subunit. Exp Dermatol. 2013;22:750-1 pubmed publisher
    ..In an in vitro model of wounding (scratches on monolayers), TNF? inhibited migration/proliferation of keratinocytes only at the edge of NMDA-R2C expressing wounded monolayers of normal keratinocytes. ..
  35. Che X, He F, Deng Y, Xu S, Fan X, Gu P, et al. HIV-1 Tat-mediated apoptosis in human blood-retinal barrier-associated cells. PLoS ONE. 2014;9:e95420 pubmed publisher
    ..Together, these findings suggest a possible mechanism and may identify a potential therapeutic strategy for HIV-1-associated ocular complications...
  36. Andersen D, Tannenberg A, Burke C, Dodd P. Developmental rearrangements of cortical glutamate-NMDA receptor binding sites in late human gestation. Brain Res Dev Brain Res. 1995;88:178-85 pubmed
    ..The evidence suggests that Glutamate-NMDA binding sites may undergo structural rearrangements which alter their ability to interact with ligands during the later stages of human gestation, and that such changes are regionally variable. ..
  37. King J, Eugenin E, Buckner C, Berman J. HIV tat and neurotoxicity. Microbes Infect. 2006;8:1347-57 pubmed
    ..This review discusses the most recent data addressing tat-induced neurotoxicity and integrates these new findings in the context of NeuroAIDS. ..
  38. Hackos D, Lupardus P, Grand T, Chen Y, Wang T, Reynen P, et al. Positive Allosteric Modulators of GluN2A-Containing NMDARs with Distinct Modes of Action and Impacts on Circuit Function. Neuron. 2016;89:983-99 pubmed publisher
  39. Chen C, Chang Y. A Simple Cell-based Immunofluorescence Assay to Detect Autoantibody Against the N-Methyl-D-Aspartate (NMDA) Receptor in Blood. J Vis Exp. 2018;: pubmed publisher
    ..1 (NR1) and one or two NMDA receptor subunit 2A (NR2A), NMDA receptor subunit 2B (NR2B), NMDA receptor subunit 2C (NR2C), or NMDA receptor subunit 2D (NR2D)...
  40. Longordo F, Feligioni M, Chiaramonte G, Sbaffi P, Raiteri M, Pittaluga A. The human immunodeficiency virus-1 protein transactivator of transcription up-regulates N-methyl-D-aspartate receptor function by acting at metabotropic glutamate receptor 1 receptors coexisting on human and rat brain noradrenergic neurones. J Pharmacol Exp Ther. 2006;317:1097-105 pubmed
    ..To conclude, Tat can represent a potent pathological agonist at mGlu1 receptors able to release acetylcholine from human cholinergic terminals and up-regulate NMDARs mediating NE release from human and rat noradrenergic terminals. ..
  41. Weickert C, Fung S, Catts V, Schofield P, Allen K, Moore L, et al. Molecular evidence of N-methyl-D-aspartate receptor hypofunction in schizophrenia. Mol Psychiatry. 2013;18:1185-92 pubmed publisher
    ..The NR1 subunit (mRNA and protein) and NR2C mRNA were decreased in postmortem brain from people with schizophrenia (P=0.004, P=0.01 and P=0.01, respectively)...
  42. Ma S, Zhuang Q, Shen W, Peng Y, Qiu Y. Interleukin-6 reduces NMDAR-mediated cytosolic Ca²⁺ overload and neuronal death via JAK/CaN signaling. Cell Calcium. 2015;58:286-95 pubmed publisher
    ..The NMDAR subunits, NR1, NR2A, NR2B and NR2C, were expressed in CGNs...
  43. Lannuzel A, Lledo P, Lamghitnia H, Vincent J, Tardieu M. HIV-1 envelope proteins gp120 and gp160 potentiate NMDA-induced [Ca2+]i increase, alter [Ca2+]i homeostasis and induce neurotoxicity in human embryonic neurons. Eur J Neurosci. 1995;7:2285-93 pubmed
    ..The neurotoxicity of picomolar doses of gp120 and gp160 cultures was estimated by immunofluorescence and colorimetric assay. Treatment of cultures with AP5 or nifedipine reduced gp120-induced toxicity by 70 and ..
  44. Dreyer E, Lipton S. The coat protein gp120 of HIV-1 inhibits astrocyte uptake of excitatory amino acids via macrophage arachidonic acid. Eur J Neurosci. 1995;7:2502-7 pubmed
    ..Our findings suggest that the observed effects on glia and neurons of gp120 may be secondary, at least in part, to its initial activation of macrophages. ..
  45. Raber J, Toggas S, Lee S, Bloom F, Epstein C, Mucke L. Central nervous system expression of HIV-1 Gp120 activates the hypothalamic-pituitary-adrenal axis: evidence for involvement of NMDA receptors and nitric oxide synthase. Virology. 1996;226:362-73 pubmed
    ..These findings demonstrate that CNS expression of a viral envelope protein can activate the HPA axis and thereby alter peripheral levels of immunomodulatory hormones. ..
  46. Lim I, Hall D, Hell J. Selectivity and promiscuity of the first and second PDZ domains of PSD-95 and synapse-associated protein 102. J Biol Chem. 2002;277:21697-711 pubmed
    ..Two of these proteins, brain-specific angiogenesis inhibitor 1 and protein kinase Calpha, co-immunoprecipitated with PSD-95 and SAP102 from rat brain extracts. ..
  47. Shi J, Badner J, Hattori E, Potash J, Willour V, McMahon F, et al. Neurotransmission and bipolar disorder: a systematic family-based association study. Am J Med Genet B Neuropsychiatr Genet. 2008;147B:1270-7 pubmed publisher
    ..system, with several reaching gene-wide significance (allelic: GRIA1, GRIN2D, and QDPR; haplotypic: GRIN2C, QDPR, and SLC6A3)...
  48. Teng H, Cai W, Zhou L, Zhang J, Liu Q, Wang Y, et al. Evolutionary mode and functional divergence of vertebrate NMDA receptor subunit 2 genes. PLoS ONE. 2010;5:e13342 pubmed publisher
    ..These findings provide intriguing subjects for testing the 2R and 3R hypothesis and we expect it could provide new insights into the underlying evolution mechanisms of cognition in vertebrate. ..
  49. Samikkannu T, Agudelo M, Gandhi N, Reddy P, Saiyed Z, Nwankwo D, et al. Human immunodeficiency virus type 1 clade B and C gp120 differentially induce neurotoxin arachidonic acid in human astrocytes: implications for neuroAIDS. J Neurovirol. 2011;17:230-8 pubmed publisher
    ..These studies suggest that HIV-1 clade B and C gp120 proteins may play a differential role in the neuropathogenesis of HAD in neuroAIDS. ..
  50. Hedegaard M, Hansen K, Andersen K, Brauner Osborne H, Traynelis S. Molecular pharmacology of human NMDA receptors. Neurochem Int. 2012;61:601-9 pubmed publisher
    ..side-by-side comparison of agonists, un-competitive antagonists, GluN2B-selective non-competitive antagonists, and GluN2C/D-selective modulators at recombinant human and rat NMDA receptors...
  51. Punnakkal P, Jendritza P, Köhr G. Influence of the intracellular GluN2 C-terminal domain on NMDA receptor function. Neuropharmacology. 2012;62:1985-92 pubmed publisher
    ..C-terminal truncation of GluN2A, GluN2B or GluN2C did not change the subunit-specific rise time but accelerated the decay time of glutamate-activated currents...
  52. Williams C, Phelps S, Porter R. Expression of Ca2+/calmodulin-dependent protein kinase types II and IV, and reduced DNA synthesis due to the Ca2+/calmodulin-dependent protein kinase inhibitor KN-62 (1-[N,O-bis(5-isoquinolinesulfonyl)-N-methyl-L-tyrosyl]-4-phenyl piperazine) in smal. Biochem Pharmacol. 1996;51:707-15 pubmed
    ..The expression of both CaMKII and CaMKIV by SCLC cells, and the sensitivity of these cells to the anti-proliferative effects of KN-62, suggest a role for CaM kinase in regulating SCLC proliferation. ..
  53. Bennett B, Rusyniak D, Hollingsworth C. HIV-1 gp120-induced neurotoxicity to midbrain dopamine cultures. Brain Res. 1995;705:168-76 pubmed
    ..These results suggest that dopaminergic neuronal damage may contribute to the manifestations of AIDS dementia complex. ..
  54. Howard S, Nakayama A, Brooke S, Sapolsky R. Glucocorticoid modulation of gp120-induced effects on calcium-dependent degenerative events in primary hippocampal and cortical cultures. Exp Neurol. 1999;158:164-70 pubmed
  55. Jaulin Bastard F, Saito H, Le Bivic A, Ollendorff V, Marchetto S, Birnbaum D, et al. The ERBB2/HER2 receptor differentially interacts with ERBIN and PICK1 PSD-95/DLG/ZO-1 domain proteins. J Biol Chem. 2001;276:15256-63 pubmed
    ..Since ERBIN and PICK1 tend to oligomerize, further complexity of protein networks may participate in ERBB2/HER2 functions and specificity. ..
  56. Karolewicz B, Stockmeier C, Ordway G. Elevated levels of the NR2C subunit of the NMDA receptor in the locus coeruleus in depression. Neuropsychopharmacology. 2005;30:1557-67 pubmed
    ..NMDAR subunit composition in the LC was evaluated in a psychiatrically normal subject. NR1 and NR2C subunit immunoreactivities in LC homogenates showed prominent bands at 120 and 135 kDa, respectively...
  57. Geeraerts T, Deiva K, M sika I, Salim H, Hery C, Tardieu M. Effects of SDF-1alpha and gp120IIIB on apoptotic pathways in SK-N-SH neuroblastoma cells. Neurosci Lett. 2006;399:115-20 pubmed
    ..SDF-1alpha enhanced NMDA activity indirectly via Src phosphorylation, whereas gp120(IIIB) probably activated the NMDA receptor directly and phosphorylated JNK. ..
  58. Chen B, Braud S, Badger J, Isaac J, Roche K. Regulation of NR1/NR2C N-methyl-D-aspartate (NMDA) receptors by phosphorylation. J Biol Chem. 2006;281:16583-90 pubmed
    b>NR2C-containing N-methyl-D-aspartate (NMDA) receptors are highly expressed in cerebellar granule cells where they mediate the majority of current in the adult...
  59. Demontis D, Nyegaard M, Buttenschøn H, Hedemand A, Pedersen C, Grove J, et al. Association of GRIN1 and GRIN2A-D with schizophrenia and genetic interaction with maternal herpes simplex virus-2 infection affecting disease risk. Am J Med Genet B Neuropsychiatr Genet. 2011;156B:913-22 pubmed publisher
    ..The aim of this study was to determine (1) whether SNP variation in the genes (GRIN1, GRIN2A, GRIN2B, GRIN2C, and GRIN2D) encoding the NMDA receptor were associated with schizophrenia; (2) whether GRIN gene variation in the ..
  60. Mocchetti I, Bachis A, Avdoshina V. Neurotoxicity of human immunodeficiency virus-1: viral proteins and axonal transport. Neurotox Res. 2012;21:79-89 pubmed publisher
    ..Moreover, these proteins have been shown to possess neurotoxic properties. This review describes new evidence of a direct interaction of the HIV protein gp120 with neurons, which might play a role in the etiopathology of HAND. ..
  61. Corasaniti M, Melino G, Navarra M, Garaci E, Finazzi Agro A, Nistico G. Death of cultured human neuroblastoma cells induced by HIV-1 gp120 is prevented by NMDA receptor antagonists and inhibitors of nitric oxide and cyclooxygenase. Neurodegeneration. 1995;4:315-21 pubmed
    ..1-10 microM). In conclusion, the present data suggest that death of human CHP100 neuroblastoma cells in culture produced by gp120 involves NO and PGE2 production. ..
  62. Toggas S, Masliah E, Mucke L. Prevention of HIV-1 gp120-induced neuronal damage in the central nervous system of transgenic mice by the NMDA receptor antagonist memantine. Brain Res. 1996;706:303-7 pubmed
    ..They also suggest that clinically tolerated NMDA receptor antagonists may be useful in the prevention of neuronal damage in HIV-1-infected patients. ..
  63. Lin Y, Bovetto S, Carver J, Giordano T. Cloning of the cDNA for the human NMDA receptor NR2C subunit and its expression in the central nervous system and periphery. Brain Res Mol Brain Res. 1996;43:57-64 pubmed
    Several overlapping cDNA clones containing 3995 nucleotides of the human 2C NMDA receptor subunit (NR2C) were isolated from human hippocampal and cerebellar cDNA libraries...
  64. Kalsi G, Whiting P, Bourdelles B, Callen D, Barnard E, Gurling H. Localization of the human NMDAR2D receptor subunit gene (GRIN2D) to 19q13.1-qter, the NMDAR2A subunit gene to 16p13.2 (GRIN2A), and the NMDAR2C subunit gene (GRIN2C) to 17q24-q25 using somatic cell hybrid and radiation hybrid mapping panels. Genomics. 1998;47:423-5 pubmed
  65. Daggett L, Johnson E, Varney M, Lin F, Hess S, Deal C, et al. The human N-methyl-D-aspartate receptor 2C subunit: genomic analysis, distribution in human brain, and functional expression. J Neurochem. 1998;71:1953-68 pubmed
    cDNAs encoding four isoforms of the human NMDA receptor (NMDAR) NMDAR2C (hNR2C-1, -2, -3, and -4) have been isolated and characterized. The overall identity of the deduced amino acid sequences of human and rat NR2C-1 is 89.0%...
  66. Bonavia R, Bajetto A, Barbero S, Albini A, Noonan D, Schettini G. HIV-1 Tat causes apoptotic death and calcium homeostasis alterations in rat neurons. Biochem Biophys Res Commun. 2001;288:301-8 pubmed
  67. Prendergast M, Rogers D, Mulholland P, Littleton J, Wilkins L, Self R, et al. Neurotoxic effects of the human immunodeficiency virus type-1 transcription factor Tat require function of a polyamine sensitive-site on the N-methyl-D-aspartate receptor. Brain Res. 2002;954:300-7 pubmed
    ..These data suggest that the neurotoxic effects of HIV-1 Tat are mediated, in part, by direct interactions with a polyamine-sensitive site on the NMDAr that positively modulates the function of this receptor. ..
  68. Self R, Mulholland P, Nath A, Harris B, Prendergast M. The human immunodeficiency virus type-1 transcription factor Tat produces elevations in intracellular Ca2+ that require function of an N-methyl-D-aspartate receptor polyamine-sensitive site. Brain Res. 2004;995:39-45 pubmed
    ..Polyamine-sensitive portions of this receptor may then represent novel therapeutic targets in the pharmacologic treatment of HAD-related neurotoxicity. ..
  69. Hynd M, Scott H, Dodd P. Differential expression of N-methyl-D-aspartate receptor NR2 isoforms in Alzheimer's disease. J Neurochem. 2004;90:913-9 pubmed
    ..lower expression of NR2A and NR2B transcripts was found in susceptible regions of AD brain, whereas expression of NR2C and NR2D transcripts did not differ from that in controls...
  70. Acker T, Yuan H, Hansen K, Vance K, Ogden K, Jensen H, et al. Mechanism for noncompetitive inhibition by novel GluN2C/D N-methyl-D-aspartate receptor subunit-selective modulators. Mol Pharmacol. 2011;80:782-95 pubmed publisher
    ..DQP-1105 inhibited GluN2C- and GluN2D-containing receptors with IC(50) values that were at least 50-fold lower than those for recombinant ..
  71. Sanz Clemente A, Nicoll R, Roche K. Diversity in NMDA receptor composition: many regulators, many consequences. Neuroscientist. 2013;19:62-75 pubmed publisher
    ..In addition, the balance between synaptic and extrasynaptic NMDARs is altered in several neuronal disorders. Here, the authors summarize the recent advances in the identification of NMDAR subunit-specific regulatory mechanisms. ..
  72. Brancaccio M, Patton A, Chesham J, Maywood E, Hastings M. Astrocytes Control Circadian Timekeeping in the Suprachiasmatic Nucleus via Glutamatergic Signaling. Neuron. 2017;93:1420-1435.e5 pubmed publisher sensed by neurons of the dorsal SCN via specific pre-synaptic NMDA receptor assemblies containing NR2C subunits...
  73. Magnuson D, Knudsen B, Geiger J, Brownstone R, Nath A. Human immunodeficiency virus type 1 tat activates non-N-methyl-D-aspartate excitatory amino acid receptors and causes neurotoxicity. Ann Neurol. 1995;37:373-80 pubmed
    ..These results suggest that Tat, released from HIV-1-infected cells, may be an important mediator of neurotoxicity observed in HIV-1 encephalopathy. ..
  74. Vissel B, Krupp J, Heinemann S, Westbrook G. Intracellular domains of NR2 alter calcium-dependent inactivation of N-methyl-D-aspartate receptors. Mol Pharmacol. 2002;61:595-605 pubmed
    ..However, inactivation is also NR2-subunit specific, because it occurs in NR2A- but not NR2C-containing receptors...
  75. Chen W, Tang Z, Fortina P, Patel P, Addya S, Surrey S, et al. Ethanol potentiates HIV-1 gp120-induced apoptosis in human neurons via both the death receptor and NMDA receptor pathways. Virology. 2005;334:59-73 pubmed
    ..Thus, these data suggest rationally-designed, molecular targets for potential anti-HIV-1 neuroprotection. ..
  76. Chen B, Roche K. Growth factor-dependent trafficking of cerebellar NMDA receptors via protein kinase B/Akt phosphorylation of NR2C. Neuron. 2009;62:471-8 pubmed publisher
    ..Although the NR2C subunit is highly enriched in cerebellar granule cells and plays a unique role in cerebellar function, little is ..
  77. Lee M, Ting K, Adams S, Brew B, Chung R, Guillemin G. Characterisation of the expression of NMDA receptors in human astrocytes. PLoS ONE. 2010;5:e14123 pubmed publisher
    ..We found that all seven currently known NMDAR subunits (NR1, NR2A, NR2B, NR2C, NR2D, NR3A and NR3B) are expressed in astrocytes, but at different levels...
  78. Shepherd A, Loo L, Mohapatra D. Chemokine co-receptor CCR5/CXCR4-dependent modulation of Kv2.1 channel confers acute neuroprotection to HIV-1 glycoprotein gp120 exposure. PLoS ONE. 2013;8:e76698 pubmed publisher
    ..These observations shed new light on the intrinsic homeostatic mechanisms of neuronal resilience during the acute stages of neuro-HIV infections. ..
  79. Chandley M, Szebeni A, Szebeni K, Crawford J, Stockmeier C, Turecki G, et al. Elevated gene expression of glutamate receptors in noradrenergic neurons from the locus coeruleus in major depression. Int J Neuropsychopharmacol. 2014;17:1569-78 pubmed publisher
    ..MDD subjects exhibited significantly higher expression levels of the NMDA receptor subunit genes, GRIN2B and GRIN2C, and the metabotropic receptor genes, GRM4 and GRM5, in LC neurons...
  80. Wayman W, Chen L, Persons A, Napier T. Cortical consequences of HIV-1 Tat exposure in rats are enhanced by chronic cocaine. Curr HIV Res. 2015;13:80-7 pubmed
    ..The brain regions and pathophysiological mechanisms that are dysregulated by both chronic cocaine and Tat are the focus of the current review. ..
  81. Chung C, Wu W, Chen B. Identification of Novel 14-3-3 Residues That Are Critical for Isoform-specific Interaction with GluN2C to Regulate N-Methyl-D-aspartate (NMDA) Receptor Trafficking. J Biol Chem. 2015;290:23188-200 pubmed publisher
    ..Previously, we have demonstrated that 14-3-3ϵ isoform dynamically regulates forward trafficking of GluN2C-containing NMDA receptors (NMDARs) in cerebellar granule neurons, that when expressed on the surface, promotes ..
  82. Wollmuth L, Kuner T, Sakmann B. Adjacent asparagines in the NR2-subunit of the NMDA receptor channel control the voltage-dependent block by extracellular Mg2+. J Physiol. 1998;506 ( Pt 1):13-32 pubmed
    ..The contribution to the blocking site, in contrast to the prevailing view, is stronger for the N + 1 site than for the N-site asparagine. The block may involve binding of Mg2+ to these residues. ..
  83. New D, Maggirwar S, Epstein L, Dewhurst S, Gelbard H. HIV-1 Tat induces neuronal death via tumor necrosis factor-alpha and activation of non-N-methyl-D-aspartate receptors by a NFkappaB-independent mechanism. J Biol Chem. 1998;273:17852-8 pubmed
  84. Hirao K, Hata Y, Ide N, Takeuchi M, Irie M, Yao I, et al. A novel multiple PDZ domain-containing molecule interacting with N-methyl-D-aspartate receptors and neuronal cell adhesion proteins. J Biol Chem. 1998;273:21105-10 pubmed
    ..We named this protein S-SCAM (synaptic scaffolding molecule) because S-SCAM may assemble receptors and cell adhesion proteins at synaptic junctions. ..
  85. Anborgh P, Qian X, Papageorge A, Vass W, DeClue J, Lowy D. Ras-specific exchange factor GRF: oligomerization through its Dbl homology domain and calcium-dependent activation of Raf. Mol Cell Biol. 1999;19:4611-22 pubmed
  86. Xin K, Hamajima K, Hattori S, Cao X, Kawamoto S, Okuda K. Evidence of HIV type 1 glycoprotein 120 binding to recombinant N-methyl-D-aspartate receptor subunits expressed in a baculovirus system. AIDS Res Hum Retroviruses. 1999;15:1461-7 pubmed
    ..These data suggest that HIV-1 gp120 may directly bind to the NMDA receptor. This evidence enhances our understanding of the mechanism of HIV-1-induced neuronal damage in AIDS patients. ..
  87. Lagrèze W, Darstein M, Feuerstein T, Otto T, Landwehrmeyer G. N-methyl-D-aspartate receptor subunit mRNA expression in human retinal ganglion cells. Graefes Arch Clin Exp Ophthalmol. 2000;238:486-90 pubmed
    ..Ninety-three percent of retinal ganglion cells expressed mRNA coding for NR1, 9% for NR2A, 28% for NR2B, 86% for NR2C, and 84% for NR2D. The pattern of expression did not vary among the five eyes...
  88. Cairns B, Svensson P, Wang K, Hupfeld S, Graven Nielsen T, Sessle B, et al. Activation of peripheral NMDA receptors contributes to human pain and rat afferent discharges evoked by injection of glutamate into the masseter muscle. J Neurophysiol. 2003;90:2098-105 pubmed
    ..It is conceivable that activation of peripheral NMDA receptors may contribute to masticatory muscle pain and that peripherally acting NMDA receptor antagonists could prove to be effective analgesics for this type of pain. ..
  89. Krapivinsky G, Krapivinsky L, Manasian Y, Ivanov A, Tyzio R, Pellegrino C, et al. The NMDA receptor is coupled to the ERK pathway by a direct interaction between NR2B and RasGRF1. Neuron. 2003;40:775-84 pubmed
    ..The specific association of RasGRF1 with the NR2B subunit and study of ERK activation in neurons with varied content of NR2B suggests that NR2B-containing channels are the dominant activators of the NMDA-dependent ERK pathway. ..
  90. Cull Candy S, Leszkiewicz D. Role of distinct NMDA receptor subtypes at central synapses. Sci STKE. 2004;2004:re16 pubmed
  91. Li W, Huang Y, Reid R, Steiner J, Malpica Llanos T, Darden T, et al. NMDA receptor activation by HIV-Tat protein is clade dependent. J Neurosci. 2008;28:12190-8 pubmed publisher
  92. Kim H, Martemyanov K, Thayer S. Human immunodeficiency virus protein Tat induces synapse loss via a reversible process that is distinct from cell death. J Neurosci. 2008;28:12604-13 pubmed publisher
    ..These results suggest that the impaired network function and decreased neuronal survival produced by Tat involve distinct mechanisms and that pharmacologic targets, such as LRP, might prove useful in restoring function in HAD patients. ..