GRIN2B | |||||||||||||||||||||||||||||||||||||||||||||||||||
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Aliases | GRIN2B, GluN2B, MRD6, NMDAR2B, NR2B, hNR3, EIEE27, glutamate ionotropic receptor NMDA type subunit 2B, NR3, DEE27 | ||||||||||||||||||||||||||||||||||||||||||||||||||
External IDs | OMIM: 138252 MGI: 95821 HomoloGene: 646 GeneCards: GRIN2B | ||||||||||||||||||||||||||||||||||||||||||||||||||
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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 of NR2B
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]
GRIN2B is one of several genes associated with neurodevelopmental disorders (NDDs),[8] including autism.[9] One study reported that approximately 30% of cases of moderate or severe intellectual disability were associated with de novo mutation (A DNA sequence difference that is not present in either parent) of such genes.[10] It has been found that expression of GRIN2B in the adult human brain is at least as high as in the developing brain.[8]
Both mice[11] and rats[12] that were engineered to over-express GRIN2B in their brains have increased mental ability. As early as 1999 it was suggested that "genetic enhancement of mental and cognitive attributes such as intelligence and memory in mammals is feasible."[11]
GRIN2B and human gene editing
The discovery that mice with the "humanized" FOXP2 have accelerated learning[13] has supported the feasibility of cognitive improvement in mammals by gene editing. Some think that GRIN2B may be an initial test case for the ethics of human gene editing,[14] since the same techniques that could be used to remove an autism-risk alelle could be used to make a change to improve cognition. Recently a committee of the USA National Academies released a consensus report[15] that gave a "yellow light" to human genome editing.[16]
Ligands
- Besonprodil
- CERC-301, a selective NR2B receptor antagonist
- Eliprodil
- Evt 101, a selective NR2B receptor antagonist. This compound was tested as a potentially fast-acting antidepressant.[17] In 2011 it was voluntarily withdrawn from a Phase II clinical study in treatment-resistant depression due to an unsatisfactory toxicity profile.[18]
- Ro-25-6981 (also known as MI-4), a selective NR2B receptor antagonist
- Traxoprodil, a selective NR2B receptor 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.
- ^ Monyer H, Sprengel R, Schoepfer R, Herb A, Higuchi M, Lomeli H, Burnashev N, Sakmann B, Seeburg PH (Jun 1992). "Heteromeric NMDA receptors: molecular and functional distinction of subtypes". Science. 256 (5060): 1217–21. doi:10.1126/science.256.5060.1217. PMID 1350383.
- ^ "Entrez Gene: GRIN2B glutamate receptor, ionotropic, N-methyl D-aspartate 2B".
- ^ Yoshimura, Yumiko; Ohmura, Tomohisa; Komatsu, Yukio (2003-07-23). "Two Forms of Synaptic Plasticity with Distinct Dependence on Age, Experience, and NMDA Receptor Subtype in Rat Visual Cortex". The Journal of Neuroscience. 23 (16): 6557–6566. ISSN 0270-6474. PMID 12878697.
- ^ a b Maussion G, Diallo AB, Gigek CO, Chen ES, Crapper L, Théroux JF, Chen GG, Vasuta C, Ernst C (2015). "Investigation of genes important in neurodevelopment disorders in adult human brain". Hum Genet. 134 (10): 1037–53. doi:10.1007/s00439-015-1584-z. PMID 26194112.
{{cite journal}}
: CS1 maint: multiple names: authors list (link) - ^ Pan Y, Chen J, Guo H, Ou J, Peng Y, Liu Q, Shen Y, Shi L, Liu Y, Xiong Z, Zhu T, Luo S, Hu Z, Zhao J, Xia K (2015). "Association of genetic variants of GRIN2B with autism". Sci Rep. 5: 8296. doi:10.1038/srep08296. PMID 25656819.
{{cite journal}}
: CS1 maint: multiple names: authors list (link) - ^ Hamdan FF, Srour M, Capo-Chichi J-M, Daoud H, Nassif C, Patry L; et al. (2014). "De Novo Mutations in Moderate or Severe Intellectual Disability". PLoS Genet. 10 (10): e1004772. doi:10.1371/journal.pgen.1004772. PMID 25356899.
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: Explicit use of et al. in:|last1=
(help)CS1 maint: multiple names: authors list (link) CS1 maint: unflagged free DOI (link) - ^ a b Tang YP, Shimizu E, Dube GR, Rampon C, Kerchner GA, Zhuo M, Liu G, Tsien JZ. (1999). "Genetic enhancement of learning and memory in mice". Nature. 401 (6748): 63–9. doi:10.1038/43432. PMID 10485705.
{{cite journal}}
: CS1 maint: multiple names: authors list (link) - ^ Wang D, Cui Z, Zeng Q, Kuang H, Wang LP, Tsien JZ, Cao X. (2009). "Genetic enhancement of memory and long-term potentiation but not CA1 long-term depression in NR2B transgenic rats". PLoS One. 4 (10): e7486. doi:10.1371/journal.pone.0007486. PMID 19838302.
{{cite journal}}
: CS1 maint: multiple names: authors list (link) CS1 maint: unflagged free DOI (link) - ^ Schreiweis C, Bornschein U, Burguière E, Kerimoglu C, Schreiter S, Dannemann M, Goyal S, Rea E, French CA, Puliyadi R, Groszer M, Fisher SE, Mundry R, Winter C, Hevers W, Pääbo S, Enard W, Graybiel AM (September 2014). "Humanized Foxp2 accelerates learning by enhancing transitions from declarative to procedural performance". Proceedings of the National Academy of Sciences of the United States of America. 111 (39): 14253–8. doi:10.1073/pnas.1414542111. PMID 25225386.
- ^ Reardon, Sara (14 February 2017). "US science advisers outline path to genetically modified babies". Nature. doi:10.1038/nature.2017.21474.
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suggested) (help) - ^ Committee on Human Gene Editing: Scientific, Medical, and Ethical Considerations. "Human Genome Editing: Science, Ethics, and Governance". nationalacademies.org. National Academy of Sciences; National Academy of Medicine. Retrieved 21 February 2017.
{{cite web}}
: CS1 maint: multiple names: authors list (link) - ^ Kaiser J (February 2017). "A yellow light for embryo editing". Science. 355 (6326): 675. doi:10.1126/science.355.6326.675-b. PMID 28209849.
- ^ "The Effects of a Novel NMDA NR2B-Subtype Selective Antagonist, EVT 101, on Brain Function". NCT00526968. ClinicalTrials.gov. 2008-02-14. Retrieved 2010-08-19.
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(help) - ^ "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.
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(help) - ^ Wyszynski M, Lin J, Rao A, Nigh E, Beggs AH, Craig AM, Sheng M (January 1997). "Competitive binding of alpha-actinin and calmodulin to the NMDA receptor". Nature. 385 (6615): 439–42. doi:10.1038/385439a0. PMID 9009191.
- ^ a b c Inanobe A, Fujita A, Ito M, Tomoike H, Inageda K, Kurachi Y (June 2002). "Inward rectifier K+ channel Kir2.3 is localized at the postsynaptic membrane of excitatory synapses". Am. J. Physiol., Cell Physiol. 282 (6): C1396-403. doi:10.1152/ajpcell.00615.2001. PMID 11997254.
- ^ a b c Irie M, Hata Y, Takeuchi M, Ichtchenko K, Toyoda A, Hirao K, Takai Y, Rosahl TW, Südhof TC (September 1997). "Binding of neuroligins to PSD-95". Science. 277 (5331): 1511–5. doi:10.1126/science.277.5331.1511. PMID 9278515.
- ^ a b c Sans N, Prybylowski K, Petralia RS, Chang K, Wang YX, Racca C, Vicini S, Wenthold RJ (June 2003). "NMDA receptor trafficking through an interaction between PDZ proteins and the exocyst complex". Nat. Cell Biol. 5 (6): 520–30. doi:10.1038/ncb990. PMID 12738960.
- ^ a b Lim IA, Hall DD, Hell JW (June 2002). "Selectivity and promiscuity of the first and second PDZ domains of PSD-95 and synapse-associated protein 102". J. Biol. Chem. 277 (24): 21697–711. doi:10.1074/jbc.M112339200. PMID 11937501.
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: CS1 maint: unflagged free DOI (link) - ^ Niethammer M, Valtschanoff JG, Kapoor TM, Allison DW, Weinberg RJ, Craig AM, Sheng M (April 1998). "CRIPT, a novel postsynaptic protein that binds to the third PDZ domain of PSD-95/SAP90". Neuron. 20 (4): 693–707. doi:10.1016/s0896-6273(00)81009-0. PMID 9581762.
- ^ 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. doi:10.1126/science.7569905. PMID 7569905.
- ^ Jo K, Derin R, Li M, Bredt DS (June 1999). "Characterization of MALS/Velis-1, -2, and -3: a family of mammalian LIN-7 homologs enriched at brain synapses in association with the postsynaptic density-95/NMDA receptor postsynaptic complex". J. Neurosci. 19 (11): 4189–99. PMID 10341223.
- ^ Nakazawa T, Watabe AM, Tezuka T, Yoshida Y, Yokoyama K, Umemori H, Inoue A, Okabe S, Manabe T, Yamamoto T (July 2003). "p250GAP, a novel brain-enriched GTPase-activating protein for Rho family GTPases, is involved in the N-methyl-d-aspartate receptor signaling". Mol. Biol. Cell. 14 (7): 2921–34. doi:10.1091/mbc.E02-09-0623. PMC 165687. 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 (2004). "The NR2B subtype of NMDA receptor: a potential target for the treatment of alcohol dependence". Curr Drug Targets CNS Neurol Disord. 3 (3): 169–79. doi:10.2174/1568007043337409. PMID 15180478.
- King JE, Eugenin EA, Buckner CM, Berman JW (2006). "HIV tat and neurotoxicity". Microbes Infect. 8 (5): 1347–57. doi:10.1016/j.micinf.2005.11.014. PMID 16697675.
- Kornau HC, Schenker LT, Kennedy MB, Seeburg PH (1995). "Domain interaction between NMDA receptor subunits and the postsynaptic density protein PSD-95". Science. 269 (5231): 1737–40. doi:10.1126/science.7569905. PMID 7569905.
- Magnuson DS, Knudsen BE, Geiger JD, Brownstone RM, Nath A (1995). "Human immunodeficiency virus type 1 tat activates non-N-methyl-D-aspartate excitatory amino acid receptors and causes neurotoxicity". Ann. Neurol. 37 (3): 373–80. doi:10.1002/ana.410370314. PMID 7695237.
- Mandich P, Schito AM, Bellone E, Antonacci R, Finelli P, Rocchi M, Ajmar F (1994). "Mapping of the human NMDAR2B receptor subunit gene (GRIN2B) to chromosome 12p12". Genomics. 22 (1): 216–8. doi:10.1006/geno.1994.1366. PMID 7959773.
- Adams SL, Foldes RL, Kamboj RK (1995). "Human N-methyl-D-aspartate receptor modulatory subunit hNR3: cloning and sequencing of the cDNA and primary structure of the protein". Biochim. Biophys. Acta. 1260 (1): 105–8. doi:10.1016/0167-4781(94)00189-a. PMID 7999784.
- Sheng M, Cummings J, Roldan LA, Jan YN, Jan LY (1994). "Changing subunit composition of heteromeric NMDA receptors during development of rat cortex". Nature. 368 (6467): 144–7. doi:10.1038/368144a0. PMID 8139656.
- Roche KW, Raymond LA, Blackstone C, Huganir RL (1994). "Transmembrane topology of the glutamate receptor subunit GluR6". J. Biol. Chem. 269 (16): 11679–82. PMID 8163463.
- Lannuzel A, Lledo PM, Lamghitnia HO, Vincent JD, Tardieu M (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". Eur. J. Neurosci. 7 (11): 2285–93. doi:10.1111/j.1460-9568.1995.tb00649.x. PMID 8563977.
- Corasaniti MT, Melino G, Navarra M, Garaci E, Finazzi-Agrò A, Nisticò G (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. doi:10.1016/1055-8330(95)90021-7. PMID 8581564.
- Niethammer M, Kim E, Sheng M (1996). "Interaction between the C terminus of NMDA receptor subunits and multiple members of the PSD-95 family of membrane-associated guanylate kinases". J. Neurosci. 16 (7): 2157–63. PMID 8601796.
- Pittaluga A, Pattarini R, Severi P, Raiteri M (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. doi:10.1097/00002030-199605000-00003. PMID 8724036.
- Hess SD, Daggett LP, Crona J, Deal C, Lu CC, Urrutia A, Chavez-Noriega L, Ellis SB, Johnson EC, Veliçelebi G (1996). "Cloning and functional characterization of human heteromeric N-methyl-D-aspartate receptors". J. Pharmacol. Exp. Ther. 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 (1996). "SAP102, a novel postsynaptic protein that interacts with NMDA receptor complexes in vivo". Neuron. 17 (2): 255–65. doi:10.1016/S0896-6273(00)80157-9. PMID 8780649.
- Wu P, Price P, Du B, Hatch WC, Terwilliger EF (1996). "Direct cytotoxicity of HIV-1 envelope protein gp120 on human NT neurons". NeuroReport. 7 (5): 1045–9. doi:10.1097/00001756-199604100-00018. PMID 8804048.
- Bennett BA, Rusyniak DE, Hollingsworth CK (1995). "HIV-1 gp120-induced neurotoxicity to midbrain dopamine cultures". Brain Res. 705 (1–2): 168–76. doi:10.1016/0006-8993(95)01166-8. PMID 8821747.
- Toggas SM, Masliah E, Mucke L (1996). "Prevention of HIV-1 gp120-induced neuronal damage in the central nervous system of transgenic mice by the NMDA receptor antagonist memantine". Brain Res. 706 (2): 303–7. doi:10.1016/0006-8993(95)01197-8. PMID 8822372.
- Dreyer EB, Lipton SA (1995). "The coat protein gp120 of HIV-1 inhibits astrocyte uptake of excitatory amino acids via macrophage arachidonic acid". Eur. J. Neurosci. 7 (12): 2502–7. doi:10.1111/j.1460-9568.1995.tb01048.x. PMID 8845955.
This article incorporates text from the United States National Library of Medicine, which is in the public domain.