Genomes and Genes
Gene Symbol: GRIN3B
Description: glutamate ionotropic receptor NMDA type subunit 3B
Alias: GluN3B, NR3B, glutamate receptor ionotropic, NMDA 3B, N-methyl-D-aspartate receptor subtype 3B, NMDA receptor subunit 3B, NMDA type glutamate receptor subunit NR3B, NMDAR3B, glutamate [NMDA] receptor subunit 3B, glutamate receptor, ionotropic, N-methyl-D-aspartate 3B
- Nishi M, Hinds H, Lu H, Kawata M, Hayashi Y. Motoneuron-specific expression of NR3B, a novel NMDA-type glutamate receptor subunit that works in a dominant-negative manner. J Neurosci. 2001;21:RC185 pubmed..This protein showed the highest similarity (51%) to the NR3A subunit of the NMDA receptor and therefore was termed NR3B. NR3B has a structure typical of glutamate receptor family members with a signal peptide and four membrane-..
- 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. ..
- Ghanbari F, Hebert Losier A, Barry J, Poirier D, Giguere V, Mader S, et al. Isolation and functional characterization of a novel endogenous inverse agonist of estrogen related receptors (ERRs) from human pregnancy urine. J Steroid Biochem Mol Biol. 2019;: pubmed publisher..ERRs) which consists of ERRα, ERRβ and ERRγ belong to the orphan nuclear receptor subfamily 3, group B (NR3B) subfamily, and are constitutively active...
- Ehsanifar M, Jafari A, Nikzad H, Zavareh M, Atlasi M, Mohammadi H, et al. Prenatal exposure to diesel exhaust particles causes anxiety, spatial memory disorders with alters expression of hippocampal pro-inflammatory cytokines and NMDA receptor subunits in adult male mice offspring. Ecotoxicol Environ Saf. 2019;176:34-41 pubmed publisher..In addition, DEPs exposed mice exhibited decreased hippocampal NR2A and NR3B expression...
- Li X, Hu P, Li Q, Zhang M, Lai Q, Wang X, et al. Correlations between the level of antibody against peptide of glutamate receptor NR3B subunit in the CSF and cognitive comorbidities of patients with epilepsy. Eur Rev Med Pharmacol Sci. 2019;23:328-337 pubmed publisher..The N-methyl-D-aspartate (NMDA) receptor subunit 3 peptide B (NR3B) modulates Mg2+ sensitivity and Ca2+ mobilization of glutamate responses in the central nervous system (CNS)...
- Tameh A, Karimian M, Zare Dehghanani Z, Aftabi Y, Beyer C. Role of Steroid Therapy after Ischemic Stroke by n-Methyl-d-Aspartate Receptor Gene Regulation. J Stroke Cerebrovasc Dis. 2018;27:3066-3075 pubmed publisher..Cerebral ischemia caused a significant downregulation in NR1, NR2A, NR2B and a profound upregulation of NR3B in cortical penumbra region...
- Hajdú T, Juhasz T, Szűcs Somogyi C, Rácz K, Zákány R. NR1 and NR3B Composed Intranuclear N-methyl-d-aspartate Receptor Complexes in Human Melanoma Cells. Int J Mol Sci. 2018;19: pubmed publisher..Western blots proved the exclusive presence of NR1 and NR3B in nuclear fractions and immunocytochemistry confirmed NR1-NR3B colocalization inside the nuclei of all melanoma ..
- Xie X, Liu H, Zhang J, Chen W, Zhuang D, Duan S, et al. Association between genetic variations of NMDA receptor NR3 subfamily genes and heroin addiction in male Han Chinese. Neurosci Lett. 2016;631:122-5 pubmed publisher..Genotyping of two SNPs (rs3739722 and rs17189632) in GRIN3A and two SNPs (rs4807399 and rs2240158) in GRIN3B was performed using TaqMan SNP genotyping method...
- Chen K, Kardys A, Chen Y, Flink S, Tabakoff B, Shih J. Altered gene expression in early postnatal monoamine oxidase A knockout mice. Brain Res. 2017;1669:18-26 pubmed publisher..were differentially expressed in P1 (upregulated: NLGN3, SLC6A2; down-regulated: HTR2C, MET, ADSL, MECP2, ALDH5A1, GRIN3B) while four autism-linked genes were differentially expressed at P7 (upregulated: HTR2B; downregulated: GRIN2D, ..
- 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)...
- Ngollo M, Lebert A, Daures M, Judes G, Rifai K, Dubois L, et al. Global analysis of H3K27me3 as an epigenetic marker in prostate cancer progression. BMC Cancer. 2017;17:261 pubmed publisher..The analysis identified ALG5, EXOSC8, CBX1, GRID2, GRIN3B, ING3, MYO1D, NPHP3-AS1, MSH6, FBXO11, SND1, SPATS2, TENM4 and TRA2A genes...
- Kumari K, Adhya A, Rath A, Reddy P, Mishra S. Estrogen-related receptors alpha, beta and gamma expression and function is associated with transcriptional repressor EZH2 in breast carcinoma. BMC Cancer. 2018;18:690 pubmed publisherOrphan nuclear receptors ERRα, ERRβ and ERRγ that belong to NR3B or type IV nuclear receptor family are well studied for their role in breast cancer pathophysiology...
- 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. ..
- 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 ..
- 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. ..
- 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. ..
- Liu H, Lin W, Liu S, Wang W, Tsai C, Wu B, et al. Genetic variation in N-methyl-D-aspartate receptor subunit NR3A but not NR3B influences susceptibility to Alzheimer's disease. Dement Geriatr Cogn Disord. 2009;28:521-7 pubmed publisher..The potential association of polymorphisms in NMDA receptor subunits NR3A and NR3B, encoded by the GRIN3A and GRIN3B genes, with AD was investigated. We performed a case-control study...
- 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. ..
- 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. ..
- 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. ..
- 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
- 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. ..
- 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. ..
- 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. ..
- 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. ..
- 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. ..
- Lammi J, Rajalin A, Huppunen J, Aarnisalo P. Cross-talk between the NR3B and NR4A families of orphan nuclear receptors. Biochem Biophys Res Commun. 2007;359:391-7 pubmedEstrogen-related receptors (NR3B family) and Nurr1, NGFI-B, and Nor1 (NR4A family) are orphan nuclear receptors lacking identified natural ligands. The mechanisms regulating their transcriptional activities have remained elusive...
- 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. ..
- Matsuno H, Ohi K, Hashimoto R, Yamamori H, Yasuda Y, Fujimoto M, et al. A naturally occurring null variant of the NMDA type glutamate receptor NR3B subunit is a risk factor of schizophrenia. PLoS ONE. 2015;10:e0116319 pubmed publisher..Here, we investigated the significance of a common human genetic variation of the NMDAR NR3B subunit that inserts 4 bases within the coding region (insCGTT) in the pathogenesis of schizophrenia...
- 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. ..
- Reitz C, Jun G, Naj A, Rajbhandary R, Vardarajan B, Wang L, et al. Variants in the ATP-binding cassette transporter (ABCA7), apolipoprotein E ?4,and the risk of late-onset Alzheimer disease in African Americans. JAMA. 2013;309:1483-92 pubmed publisher..Identification of disease-associated variants helps identify targets for genetic testing, prevention, and treatment...
- 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. ..
- 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...
- 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..gp 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. ..
- 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. ..
- 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. ..
- 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
- 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. ..
- 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. ..
- Johar A, Mastronardi C, Rojas Villarraga A, Patel H, Chuah A, Peng K, et al. Novel and rare functional genomic variants in multiple autoimmune syndrome and SjÃ¶gren's syndrome. J Transl Med. 2015;13:173 pubmed publisher..were identified in cases but not in controls, harboured in: MACF1, KIAA0754, DUSP12, ICA1, CELA1, LRP1/STAT6, GRIN3B, ANKLE1, TMEM161A, and FKRP...
- Xu H, Bae M, Tovar Y Romo L, Patel N, Bandaru V, Pomerantz D, et al. The human immunodeficiency virus coat protein gp120 promotes forward trafficking and surface clustering of NMDA receptors in membrane microdomains. J Neurosci. 2011;31:17074-90 pubmed publisher..These findings demonstrate that gp120 contributes to synaptic dysfunction in the setting of HIV infection by interfering with NMDA receptor trafficking...
- Hornig T, Grüning B, Kundu K, Houwaart T, Backofen R, Biber K, et al. GRIN3B missense mutation as an inherited risk factor for schizophrenia: whole-exome sequencing in a family with a familiar history of psychotic disorders. Genet Res (Camb). 2017;99:e1 pubmed publisher..this highly affected family, we found a frameshift mutation (rs10666583) in the GRIN3B gene, which codes for the GluN3B subunit of the NMDA receptor in all family members with a psychotic disorder, but not in the healthy relatives...
- Novotný J, Chughtai A, Kostrouchová M, Kostrouchová V, Kostrouch D, Kaššák F, et al. Trichoplax adhaerens reveals a network of nuclear receptors sensitive to 9-cis-retinoic acid at the base of metazoan evolution. Peerj. 2017;5:e3789 pubmed publisher..Grell) includes four nuclear receptors, namely orthologue of RXR (NR2B), HNF4 (NR2A), COUP-TF (NR2F) and ERR (NR3B) that show a high degree of similarity with human orthologues...
- 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. ..
- 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. ..
- 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