GRIN2B
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| Location (UCSC) | Chr 12: 13.44 – 13.98 Mb | Chr 6: 135.69 – 136.15 Mb | |||||||
| PubMed search | [3] | [4] | |||||||
| View/Edit Human | View/Edit Mouse |
Glutamate [NMDA] receptor subunit epsilon-2, also known as N-methyl D-aspartate receptor subtype 2B (NMDAR2B or NR2B), is a protein that in humans is encoded by the GRIN2B gene.[5]
NMDA receptors
N-methyl-D-aspartate (NMDA) receptors are a class of ionotropic glutamate receptors. The NMDA receptor channel has been shown to be involved in long-term potentiation, an activity-dependent increase in the efficiency of synaptic transmission thought to underlie certain kinds of memory and learning. NMDA receptor channels are heterotetramers composed of two molecules of the key receptor subunit NMDAR1 (GRIN1) and two drawn from one or more of the four NMDAR2 subunits: NMDAR2A (GRIN2A), NMDAR2B (GRIN2B), NMDAR2C (GRIN2C), and NMDAR2D (GRIN2D). The NR2 subunit acts as the agonist binding site for glutamate, one of the predominant excitatory neurotransmitter receptors in the mammalian brain.[6]
Function
NR2B has been associated with age- and visual-experience-dependent plasticity in the neocortex of rats, where an increased NR2B/NR2A ratio correlates directly with the stronger excitatory LTP in young animals. This is thought to contribute to experience-dependent refinement of developing cortical circuits.[7]
Engineered to overexpress GRIN2B in their brains, mice and rats exhibit improved mental function. The "Doogie" mouse performed twice as well on one learning test.[8][9]
Ligands
- Besonprodil
- CERC-301, a selective NR2B receptor antagonist
- Eliprodil
- STEP, leading to reduced receptor function
- Ifenprodil
- Rislenemdaz
- EVT-101, a selective NR2B receptor antagonist. This compound was tested as a potentially fast-acting antidepressant.[10] In 2011 it was voluntarily withdrawn from a Phase II clinical study in treatment-resistant depression due to an unsatisfactory toxicity profile.[11]
- positive allosteric modulator for the GABAA receptor
- Ro-25-6981 (also known as MI-4), a selective NR2B receptor antagonist
- Traxoprodil, a selective NR2B receptor antagonist
- Toluene - noncompetitive antagonist
Interactions
GRIN2B has been shown to
interact
with:
See also
References
- ^ a b c GRCh38: Ensembl release 89: ENSG00000273079 – Ensembl, May 2017
- ^ a b c GRCm38: Ensembl release 89: ENSMUSG00000030209 – Ensembl, May 2017
- ^ "Human PubMed Reference:". National Center for Biotechnology Information, U.S. National Library of Medicine.
- ^ "Mouse PubMed Reference:". National Center for Biotechnology Information, U.S. National Library of Medicine.
- S2CID 989677.
- ^ "Entrez Gene: GRIN2B glutamate receptor, ionotropic, N-methyl D-aspartate 2B".
- PMID 12878697.
- S2CID 481884.
- PMID 19838302.
- ^ Fuder, Dr Hermann (2008-02-14). "The Effects of a Novel NMDA NR2B-Subtype Selective Antagonist, EVT 101, on Brain Function". Nct00526968. ClinicalTrials.gov. Retrieved 2010-08-19.
- ^ "Phase II study with NR2B sub-type selective NMDA antagonist in treatment-resistant depression voluntarily terminated". evotec.com. 2011-05-18. Retrieved 2015-08-24.[permanent dead link]
- S2CID 4266742.
- ^ PMID 11997254.
- ^ PMID 9278515.
- ^ S2CID 13444388.
- ^ PMID 11937501.
- S2CID 16068361.
- PMID 7569905.
- PMID 10341223.
- PMID 12857875.
Further reading
- Schröder HC, Perovic S, Kavsan V, Ushijima H, Müller WE (1998). "Mechanisms of prionSc- and HIV-1 gp120 induced neuronal cell death". Neurotoxicology. 19 (4–5): 683–8. PMID 9745929.
- Nagy J (June 2004). "The NR2B subtype of NMDA receptor: a potential target for the treatment of alcohol dependence". Current Drug Targets. CNS and Neurological Disorders. 3 (3): 169–79. PMID 15180478.
- King JE, Eugenin EA, Buckner CM, Berman JW (April 2006). "HIV tat and neurotoxicity". Microbes and Infection. 8 (5): 1347–57. PMID 16697675.
- Kornau HC, Schenker LT, Kennedy MB, Seeburg PH (September 1995). "Domain interaction between NMDA receptor subunits and the postsynaptic density protein PSD-95". Science. 269 (5231): 1737–40. PMID 7569905.
- Magnuson DS, Knudsen BE, Geiger JD, Brownstone RM, Nath A (March 1995). "Human immunodeficiency virus type 1 tat activates non-N-methyl-D-aspartate excitatory amino acid receptors and causes neurotoxicity". Annals of Neurology. 37 (3): 373–80. S2CID 24405132.
- Mandich P, Schito AM, Bellone E, Antonacci R, Finelli P, Rocchi M, Ajmar F (July 1994). "Mapping of the human NMDAR2B receptor subunit gene (GRIN2B) to chromosome 12p12". Genomics. 22 (1): 216–8. PMID 7959773.
- Adams SL, Foldes RL, Kamboj RK (January 1995). "Human N-methyl-D-aspartate receptor modulatory subunit hNR3: cloning and sequencing of the cDNA and primary structure of the protein". Biochimica et Biophysica Acta. 1260 (1): 105–8. PMID 7999784.
- Sheng M, Cummings J, Roldan LA, Jan YN, Jan LY (March 1994). "Changing subunit composition of heteromeric NMDA receptors during development of rat cortex". Nature. 368 (6467): 144–7. S2CID 4332025.
- Roche KW, Raymond LA, Blackstone C, Huganir RL (April 1994). "Transmembrane topology of the glutamate receptor subunit GluR6". The Journal of Biological Chemistry. 269 (16): 11679–82. PMID 8163463.
- Lannuzel A, Lledo PM, Lamghitnia HO, Vincent JD, Tardieu M (November 1995). "HIV-1 envelope proteins gp120 and gp160 potentiate NMDA-induced [Ca2+]i increase, alter [Ca2+]i homeostasis and induce neurotoxicity in human embryonic neurons". The European Journal of Neuroscience. 7 (11): 2285–93. S2CID 27201873.
- Corasaniti MT, Melino G, Navarra M, Garaci E, Finazzi-Agrò A, Nisticò G (September 1995). "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. 4 (3): 315–21. PMID 8581564.
- Niethammer M, Kim E, Sheng M (April 1996). "Interaction between the C terminus of NMDA receptor subunits and multiple members of the PSD-95 family of membrane-associated guanylate kinases". The Journal of Neuroscience. 16 (7): 2157–63. PMID 8601796.
- Pittaluga A, Pattarini R, Severi P, Raiteri M (May 1996). "Human brain N-methyl-D-aspartate receptors regulating noradrenaline release are positively modulated by HIV-1 coat protein gp120". AIDS. 10 (5): 463–8. S2CID 1669986.
- Hess SD, Daggett LP, Crona J, Deal C, Lu CC, Urrutia A, Chavez-Noriega L, Ellis SB, Johnson EC, Veliçelebi G (August 1996). "Cloning and functional characterization of human heteromeric N-methyl-D-aspartate receptors". The Journal of Pharmacology and Experimental Therapeutics. 278 (2): 808–16. PMID 8768735.
- Müller BM, Kistner U, Kindler S, Chung WJ, Kuhlendahl S, Fenster SD, Lau LF, Veh RW, Huganir RL, Gundelfinger ED, Garner CC (August 1996). "SAP102, a novel postsynaptic protein that interacts with NMDA receptor complexes in vivo". Neuron. 17 (2): 255–65. S2CID 18715321.
- Wu P, Price P, Du B, Hatch WC, Terwilliger EF (April 1996). "Direct cytotoxicity of HIV-1 envelope protein gp120 on human NT neurons". NeuroReport. 7 (5): 1045–9. S2CID 21018147.
- Bennett BA, Rusyniak DE, Hollingsworth CK (December 1995). "HIV-1 gp120-induced neurotoxicity to midbrain dopamine cultures". Brain Research. 705 (1–2): 168–76. S2CID 32822686.
- Toggas SM, Masliah E, Mucke L (January 1996). "Prevention of HIV-1 gp120-induced neuronal damage in the central nervous system of transgenic mice by the NMDA receptor antagonist memantine". Brain Research. 706 (2): 303–7. S2CID 44260060.
- Dreyer EB, Lipton SA (December 1995). "The coat protein gp120 of HIV-1 inhibits astrocyte uptake of excitatory amino acids via macrophage arachidonic acid". The European Journal of Neuroscience. 7 (12): 2502–7. S2CID 7370984.
This article incorporates text from the United States National Library of Medicine, which is in the public domain.