A naturally occurring null variant of the NMDA type glutamate receptor NR3B subunit is a risk factor of schizophrenia

PLoS ONE

Volumn 10, Issue 3, 2015, Pages

  Matsuno, Hitomi ^a   Ohi, Kazutaka ^b   Hashimoto, Ryota ^b,c   Yamamori, Hidenaga ^b   Yasuda, Yuka ^b   Fujimoto, Michiko ^b   Yano Umeda, Satomi ^b   Saneyoshi, Takeo ^a   Takeda, Masatoshi ^b   Hayashi, Yasunori ^a,d  

^a RIKEN BRAIN SCIENCE INSTITUTE   (Japan)

^b OSAKA UNIVERSITY GRADUATE SCHOOL OF MEDICINE   (Japan)

^c OSAKA UNIVERSITY   (Japan)

^d SAITAMA UNIVERSITY   (Japan)

Author keywords

[No Author keywords available]

Indexed keywords

N METHYL DEXTRO ASPARTIC ACID RECEPTOR; NMDA TYPE GLUTAMATE RECEPTOR NR3B SUBUNIT; UNCLASSIFIED DRUG; NR3B NMDA RECEPTOR;

ADULT; ARTICLE; CELL SURFACE; CONTROLLED STUDY; EDUCATIONAL STATUS; FEMALE; GENE; GENE FREQUENCY; GENETIC ANALYSIS; GENETIC ASSOCIATION; GENETIC CODE; GENETIC PREDISPOSITION; GENETIC RISK; GENETIC VARIABILITY; GENOTYPE; HUMAN; INTELLIGENCE QUOTIENT; JAPAN; LOSS OF FUNCTION MUTATION; MAJOR CLINICAL STUDY; MALE; NR3B GENE; NULL ALLELE; PATHOGENESIS; PROTEIN EXPRESSION; PROTEIN LOCALIZATION; PROTEIN STRUCTURE; RISK FACTOR; SCHIZOTYPAL PERSONALITY DISORDER; CASE CONTROL STUDY; GENETIC ASSOCIATION STUDY; GENETICS; MIDDLE AGED; PATHOLOGY; SCHIZOPHRENIA; SINGLE NUCLEOTIDE POLYMORPHISM;

ADULT; CASE-CONTROL STUDIES; FEMALE; GENE FREQUENCY; GENETIC ASSOCIATION STUDIES; GENETIC PREDISPOSITION TO DISEASE; GENOTYPE; HUMANS; MALE; MIDDLE AGED; POLYMORPHISM, SINGLE NUCLEOTIDE; RECEPTORS, N-METHYL-D-ASPARTATE; SCHIZOPHRENIA;

EID: 84930505069     PISSN: None     EISSN: 19326203     Source Type: Journal    
DOI: 10.1371/journal.pone.0116319     Document Type: Article

References (65)

1. Pulay AJ, Stinson FS, Dawson DA, Goldstein RB, Chou SP, et al. (2009) Prevalence, correlates, disability, and comorbidity of DSM-IV schizotypal personality disorder: results from the wave 2 national epidemiologic survey on alcohol and related conditions. Prim Care Companion J Clin Psychiatry 11: 53-67. PMID: 19617934
2. Snyder MA, Gao WJ (2013) NMDA hypofunction as a convergence point for progression and symptoms of schizophrenia. Front Cell Neurosci 7: 31. doi: 10.3389/fncel.2013.00031 PMID: 23543703
3. Anis NA, Berry SC, Burton NR, Lodge D (1983) The dissociative anaesthetics, ketamine and phencyclidine, selectively reduce excitation of central mammalian neurones by N-methyl-aspartate. Br J Pharmacol 79: 565-575. PMID: 6317114
4. Javitt DC, Zukin SR (1991) Recent advances in the phencyclidine model of schizophrenia. Am J Psychiatry 148: 1301-1308. PMID: 1654746
5. Mohn AR, Gainetdinov RR, Caron MG, Koller BH (1999) Mice with reduced NMDA receptor expression display behaviors related to schizophrenia. Cell 98: 427-436. doi: 10.1016/S0092-8674(00)81972-8 PMID: 10481908
6. Belforte JE, Zsiros V, Sklar ER, Jiang Z, Yu G, et al. (2010) Postnatal NMDA receptor ablation in corticolimbic interneurons confers schizophrenia-like phenotypes. Nat Neurosci 13: 76-83. doi: 10.1038/nn.2447 PMID: 19915563
7. Akbarian S, Sucher NJ, Bradley D, Tafazzoli A, Trinh D, et al. (1996) Selective alterations in gene expression for NMDA receptor subunits in prefrontal cortex of schizophrenics. J Neurosci 16: 19-30. PMID: 8613785
8. Cioffi CL (2013) Modulation of NMDA receptor function as a treatment for schizophrenia. Bioorg Med Chem Lett 23: 5034-5044. doi: 10.1016/j.bmcl.2013.07.019 PMID: 23916256
9. Traynelis SF, Wollmuth LP, McBain CJ, Menniti FS, Vance KM, et al. (2010) Glutamate receptor ion channels: structure, regulation, and function. Pharmacol Rev 62: 405-496. doi: 10.1124/pr.109.002451 PMID: 20716669
10. Ciabarra AM, Sullivan JM, Gahn LG, Pecht G, Heinemann S, et al. (1995) Cloning and characterization of chi-1: a developmentally regulated member of a novel class of the ionotropic glutamate receptor family. J Neurosci 15: 6498-6508. PMID: 7472412
11. Sucher NJ, Akbarian S, Chi CL, Leclerc CL, Awobuluyi M, et al. (1995) Developmental and regional expression pattern of a novel NMDA receptor- like subunit (NMDAR-L) in the rodent brain. J Neurosci 15: 6509-6520. PMID: 7472413
12. Nishi M, Hinds H, Lu HP, Kawata M, Hayashi Y (2001) Motoneuron-specific expression of NR3B, a novel NMDA-type glutamate receptor subunit that works in a dominant-negative manner. J Neurosci 21: RC185. PMID: 11717388
13. Chatterton JE, Awobuluyi M, Premkumar LS, Takahashi H, Talantova M, et al. (2002) Excitatory glycine receptors containing the NR3 family of NMDA receptor subunits. Nature 415: 793-798. doi: 10.1038/nature715 PMID: 11823786
14. Riley B, Kendler KS (2006) Molecular genetic studies of schizophrenia. Eur J Hum Genet 14: 669-680. doi: 10.1038/sj.ejhg.5201571 PMID: 16721403
15. Begni S, Moraschi S, Bignotti S, Fumagalli F, Rillosi L, et al. (2003) Association between the G1001C polymorphism in the GRIN1 gene promoter region and schizophrenia. Biol Psychiatry 53: 617-619. doi: 10.1016/S0006-3223(02)01783-3 PMID: 12679240
16. Galehdari H, Pooryasin A, Foroughmand A, Daneshmand S, Saadat M (2009) Association between the G1001C polymorphism in the GRIN1 gene promoter and schizophrenia in the Iranian population. J Mol Neurosci 38: 178-181. doi: 10.1007/s12031-008-9148-5 PMID: 18792810
17. Martucci L, Wong AH, De Luca V, Likhodi O, Wong GW, et al. (2006) N-methyl-D-aspartate receptor NR2B subunit gene GRIN2B in schizophrenia and bipolar disorder: Polymorphisms and mRNA levels. Schizophr Res 84: 214-221. doi: 10.1016/j.schres.2006.02.001 PMID: 16549338
18. Qin S, Zhao X, Pan Y, Liu J, Feng G, et al. (2005) An association study of the N-methyl-D-aspartate receptor NR1 subunit gene (GRIN1) and NR2B subunit gene (GRIN2B) in schizophrenia with universal DNA microarray. Eur J Hum Genet 13: 807-814. doi: 10.1038/sj.ejhg.5201418 PMID: 15841096
19. Allen NC, Bagade S, McQueen MB, Ioannidis JP, Kavvoura FK, et al. (2008) Systematic meta-analyses and field synopsis of genetic association studies in schizophrenia: the SzGene database. Nat Genet 40: 827-834. doi: 10.1038/ng.171 PMID: 18583979
20. Tarabeux J, Kebir O, Gauthier J, Hamdan FF, Xiong L, et al. (2011) Rare mutations in N-methyl-D-aspartate glutamate receptors in autism spectrum disorders and schizophrenia. Transl Psychiatry 1: e55. doi: 10.1038/tp.2011.52 PMID: 22833210
21. Takata A, Iwayama Y, Fukuo Y, Ikeda M, Okochi T, et al. (2013) A population-specific uncommon variant in GRIN3A associated with schizophrenia. Biol Psychiatry 73: 532-539. doi: 10.1016/j.biopsych.2012.10.024 PMID: 23237318
22. Matsuda K, Kamiya Y, Matsuda S, Yuzaki M (2002) Cloning and characterization of a novel NMDA receptor subunit NR3B: a dominant subunit that reduces calcium permeability. Brain Res Mol Brain Res 100: 43-52. PMID: 12008020
23. Fukaya M, Hayashi Y, Watanabe M (2005) NR2 to NR3B subunit switchover of NMDA receptors in early postnatal motoneurons. Eur J Neurosci 21: 1432-1436. doi: 10.1111/j.1460-9568.2005.03957.x PMID: 15813953
24. Low CM, Wee KS (2010) New insights into the not-so-new NR3 subunits of N-methyl-D-aspartate receptor: localization, structure, and function. Mol Pharmacol 78: 1-11. doi: 10.1124/mol.110.064006 PMID: 20363861
25. Andersson O, Stenqvist A, Attersand A, von Euler G (2001) Nucleotide sequence, genomic organization, and chromosomal localization of genes encoding the human NMDA receptor subunits NR3A and NR3B. Genomics 78: 178-184. doi: 10.1006/geno.2001.6666 PMID: 11735224
26. Bendel O, Meijer B, Hurd Y, von Euler G (2005) Cloning and expression of the human NMDA receptor subunit NR3B in the adult human hippocampus. Neurosci Lett 377: 31-36. doi: 10.1016/j.neulet.2004.11.064 PMID: 15722182
27. Niemann S, Landers JE, Churchill MJ, Hosler B, Sapp P, et al. (2008) Motoneuron-specific NR3B gene: no association with ALS and evidence for a common null allele. Neurology 70: 666-676. doi: 10.1212/01.wnl.0000271078.51280.17 PMID: 17687115
28. Niemann S, Kanki H, Fukui Y, Takao K, Fukaya M, et al. (2007) Genetic ablation of NMDA receptor subunit NR3B in mouse reveals motoneuronal and nonmotoneuronal phenotypes. Eur J Neurosci 26: 1407-1420. doi: 10.1111/j.1460-9568.2007.05774.x PMID: 17880385
29. Smothers CT, Woodward JJ (2009) Expression of glycine-activated diheteromeric NR1/NR3 receptors in human embryonic kidney 293 cells Is NR1 splice variant-dependent. J Pharmacol Exp Ther 331: 975-984. doi: 10.1124/jpet.109.158493 PMID: 19726695
30. Fukumori R, Takarada T, Nakamichi N, Kambe Y, Kawagoe H, et al. (2010) Requirement of both NR3A and NR3B subunits for dominant negative properties on Ca2+ mobilization mediated by acquired Nmethyl-D-aspartate receptor channels into mitochondria. Neurochem Int 57: 730-737. doi: 10.1016/j.neuint.2010.08.009 PMID: 20813147
31. Shi SH, Hayashi Y, Petralia RS, Zaman SH, Wenthold RJ, et al. (1999) Rapid spine delivery and redistribution of AMPA receptors after synaptic NMDA receptor activation. Science 284: 1811-1816. doi: 10.1126/science.284.5421.1811 PMID: 10364548
32. Niwa H, Yamamura K, Miyazaki J (1991) Efficient selection for high-expression transfectants with a novel eukaryotic vector. Gene 108: 193-199. PMID: 1660837
33. Matsuda K, Fletcher M, Kamiya Y, Yuzaki M (2003) Specific assembly with the NMDA receptor 3B subunit controls surface expression and calcium permeability of NMDA receptors. J Neurosci 23: 10064-10073. PMID: 14602821
34. Wee KS, Wee ZN, Chow NB, Low CM (2010) The distal carboxyl terminal of rat NR3B subunit regulates NR1-1a/NR3B and NR1-2a/NR3B surface trafficking. Neurochem Int 57: 97-101. doi: 10.1016/j.neuint.2010.05.003 PMID: 20466026
35. Hashimoto R, Hashimoto H, Shintani N, Chiba S, Hattori S, et al. (2007) Pituitary adenylate cyclase-activating polypeptide is associated with schizophrenia. Molecular Psychiatry 12: 1026-1032. doi: 10.1038/sj.mp.4001982 PMID: 17387318
36. Hashimoto R, Numakawa T, Ohnishi T, Kumamaru E, Yagasaki Y, et al. (2006) Impact of the DISC1 Ser704Cys polymorphism on risk for major depression, brain morphology and ERK signaling. Human Molecular Genetics 15: 3024-3033. doi: 10.1093/hmg/ddl244 PMID: 16959794
37. Iijima Y, Sasaki J, Bando N, Asai T, Mouri I, et al. (2010) Development of a Japanese version of the schizotypal personality questionnaire and factor structure of schizotypy. Koudouryouhoukenkyu 36: 29-41.
38. Someya T, Sasaki T, Takahashi S (1994) Reliability and validity of schizotypal personality questionnaire (in Japanese). The Proceeding of the 32nd Scientific Meeting of the University Health Care in Japan 286-290.
39. Raine A (1991) The SPQ: a scale for the assessment of schizotypal personality based on DSM-III-R criteria. Schizophr Bull 17: 555-564. PMID: 1805349
40. Raine A, Reynolds C, Lencz T, Scerbo A, Triphon N, et al. (1994) Cognitive-perceptual, interpersonal, and disorganized features of schizotypal personality. Schizophr Bull 20: 191-201. PMID: 8197415
41. Moriwaki M, Kishi T, Takahashi H, Hashimoto R, Kawashima K, et al. (2009) Prepulse inhibition of the startle response with chronic schizophrenia: a replication study. Neurosci Res 65: 259-262. doi: 10.1016/j.neures.2009.07.009 PMID: 19660506
42. Takahashi H, Iwase M, Canuet L, Yasuda Y, Ohi K, et al. (2010) Relationship between prepulse inhibition of acoustic startle response and schizotypy in healthy Japanese subjects. Psychophysiology 47: 831-837. doi: 10.1111/j.1469-8986.2010.01000.x PMID: 20233344
43. Takahashi H, Iwase M, Ishii R, Ohi K, Fukumoto M, et al. (2008) Impaired prepulse inhibition and habituation of acoustic startle response in Japanese patients with schizophrenia. Neurosci Res 62: 187-194. doi: 10.1016/j.neures.2008.08.006 PMID: 18789980
44. Hashimoto R, Ohi K, Yasuda Y, Fukumoto M, Yamamori H, et al. (2011) Variants of the RELA gene are associated with schizophrenia and their startle responses. Neuropsychopharmacology 36: 1921-1931. doi: 10.1038/npp.2011.78 PMID: 21593732
45. Koide T, Banno M, Aleksic B, Yamashita S, Kikuchi T, et al. (2012) Common variants in MAGI2 gene are associated with increased risk for cognitive impairment in schizophrenic patients. PLoS One 7: e36836. doi: 10.1371/journal.pone.0036836 PMID: 22649501
46. Banno M, Koide T, Aleksic B, Yamada K, Kikuchi T, et al. (2011) A case control association study and cognitive function analysis of neuropilin and tolloid-like 1 gene and schizophrenia in the Japanese population. PLoS One 6: e28929. doi: 10.1371/journal.pone.0028929 PMID: 22205981
47. Meddows E, Le Bourdelles B, Grimwood S, Wafford K, Sandhu S, et al. (2001) Identification of molecular determinants that are important in the assembly of N-methyl-D-aspartate receptors. J Biol Chem 276: 18795-18803. doi: 10.1074/jbc.M101382200 PMID: 11279200
48. Fujiki Y, Hubbard AL, Fowler S, Lazarow PB (1982) Isolation of intracellular membranes by means of sodium carbonate treatment: application to endoplasmic reticulum. J Cell Biol 93: 97-102. doi: 10.1083/jcb.93.1.97 PMID: 7068762
49. Gielen M, Siegler Retchless B, Mony L, Johnson JW, Paoletti P (2009) Mechanism of differential control of NMDA receptor activity by NR2 subunits. Nature 459: 703-707. doi: 10.1038/nature07993 PMID: 19404260
50. O'Brien RJ, Xu D, Petralia RS, Steward O, Huganir RL, et al. (1999) Synaptic clustering of AMPA receptors by the extracellular immediate-early gene product Narp. Neuron 23: 309-323. doi: 10.1016/S0896-6273(00)80782-5 PMID: 10399937
51. Baker KE, Parker R (2004) Nonsense-mediated mRNA decay: terminating erroneous gene expression. Curr Opin Cell Biol 16: 293-299. doi: 10.1016/j.ceb.2004.03.003 PMID: 15145354
52. Wee KS, Zhang Y, Khanna S, Low CM (2008) Immunolocalization of NMDA receptor subunit NR3B in selected structures in the rat forebrain, cerebellum, and lumbar spinal cord. J Comp Neurol 509: 118-135. doi: 10.1002/cne.21747 PMID: 18425811
53. International Schizophrenia C, Purcell SM, Wray NR, Stone JL, Visscher PM, et al. (2009) Common polygenic variation contributes to risk of schizophrenia and bipolar disorder. Nature 460: 748-752. doi: 10.1038/nature08185 PMID: 19571811
54. Avramopoulos D, Stefanis NC, Hantoumi I, Smyrnis N, Evdokimidis I, et al. (2002) Higher scores of self reported schizotypy in healthy young males carrying the COMT high activity allele. Mol Psychiatry 7: 706-711. doi: 10.1038/sj.mp.4001070 PMID: 12192614
55. Schurhoff F, Szoke A, Chevalier F, Roy I, Meary A, et al. (2007) Schizotypal dimensions: an intermediate phenotype associated with the COMT high activity allele. Am J Med Genet B Neuropsychiatr Genet 144B: 64-68. doi: 10.1002/ajmg.b.30395 PMID: 17034018
56. Sheldrick AJ, Krug A, Markov V, Leube D, Michel TM, et al. (2008) Effect of COMT val158met genotype on cognition and personality. Eur Psychiatry 23: 385-389. doi: 10.1016/j.eurpsy.2008.05.002 PMID: 18755576
57. Kircher T, Markov V, Krug A, Eggermann T, Zerres K, et al. (2009) Association of the DTNBP1 genotype with cognition and personality traits in healthy subjects. Psychol Med 39: 1657-1665. doi: 10.1017/S0033291709005388 PMID: 19335929
58. Stefanis NC, Trikalinos TA, Avramopoulos D, Smyrnis N, Evdokimidis I, et al. (2007) Impact of schizophrenia candidate genes on schizotypy and cognitive endophenotypes at the population level. Biol Psychiatry 62: 784-792. doi: 10.1016/j.biopsych.2006.11.015 PMID: 17336946
59. Yasuda Y, Hashimoto R, Ohi K, Fukumoto M, Umeda-Yano S, et al. (2011) Impact on schizotypal personality trait of a genome-wide supported psychosis variant of the ZNF804A gene. Neurosci Lett 495: 216-220. doi: 10.1016/j.neulet.2011.03.069 PMID: 21457757
60. Hong LE, Wonodi I, Stine OC, Mitchell BD, Thaker GK (2008) Evidence of missense mutations on the neuregulin 1 gene affecting function of prepulse inhibition. Biol Psychiatry 63: 17-23. doi: 10.1016/j.biopsych.2007.05.011 PMID: 17631867
61. Quednow BB, Wagner M, Mossner R, Maier W, Kuhn KU (2010) Sensorimotor gating of schizophrenia patients depends on Catechol O-methyltransferase Val158Met polymorphism. Schizophr Bull 36: 341-346. doi: 10.1093/schbul/sbn088 PMID: 18635674
62. Quednow BB, Kuhn KU, Mossner R, Schwab SG, Schuhmacher A, et al. (2008) Sensorimotor gating of schizophrenia patients is influenced by 5-HT2A receptor polymorphisms. Biol Psychiatry 64: 434-437. doi: 10.1016/j.biopsych.2008.02.019 PMID: 18420180
63. Egan MF, Goldberg TE, Kolachana BS, Callicott JH, Mazzanti CM, et al. (2001) Effect of COMT Val108/158 Met genotype on frontal lobe function and risk for schizophrenia. Proc Natl Acad Sci U S A 98: 6917-6922. doi: 10.1073/pnas.111134598 PMID: 11381111
64. Lin YT, Hsieh MH, Liu CC, Hwang TJ, Chien YL, et al. (2014) A recently-discovered NMDA receptor gene, GRIN3B, is associated with duration mismatch negativity. Psychiatry Res 218: 356-358. doi: 10.1016/j.psychres.2014.04.032 PMID: 24814139
65. Niemann S, Landers JE, Churchill MJ, Hosler B, Sapp P, et al. (2008) Motoneuron-specific NR3B gene: no association with ALS and evidence for a common null allele. Neurology 70: 666-676. PMID: 17687115