GRIN1 explained

Glutamate [NMDA] receptor subunit zeta-1 is a protein that in humans is encoded by the GRIN1 gene.^{[1] [2]}

The protein encoded by this gene is a critical subunit of N-methyl-D-aspartate receptors, members of the glutamate receptor channel superfamily which are heteromeric protein complexes with multiple subunits arranged to form a ligand-gated ion channel. These subunits play a key role in the plasticity of synapses, which is believed to underlie memory and learning. The gene consists of 21 exons and is alternatively spliced, producing transcript variants differing in the C-terminus. The sequence of exon 5 is identical in vertebrates, with exon 5 splicing demonstrated in human, mouse and rat.^{[3] [4] [5] [6]} Cell-specific factors are thought to control expression of different isoforms, possibly contributing to the functional diversity of the subunits.^[2]

See also

• NMDA receptor

References

Further reading

• Lin JW, Wyszynski M, Madhavan R, Sealock R, Kim JU, Sheng M . Yotiao, a novel protein of neuromuscular junction and brain that interacts with specific splice variants of NMDA receptor subunit NR1 . The Journal of Neuroscience . 18 . 6 . 2017–2027 . March 1998 . 9482789 . 6792910 . 10.1523/JNEUROSCI.18-06-02017.1998 .
• Schröder HC, Perovic S, Kavsan V, Ushijima H, Müller WE . Mechanisms of prionSc- and HIV-1 gp120 induced neuronal cell death . Neurotoxicology . 19 . 4–5 . 683–688 . 1998 . 9745929 .
• Adriani W, Felici A, Sargolini F, Roullet P, Usiello A, Oliverio A, Mele A . N-methyl-D-aspartate and dopamine receptor involvement in the modulation of locomotor activity and memory processes . Experimental Brain Research . 123 . 1–2 . 52–59 . November 1998 . 9835392 . 10.1007/s002210050544 . 8388670 .
• Dingledine R, Borges K, Bowie D, Traynelis SF . The glutamate receptor ion channels . Pharmacological Reviews . 51 . 1 . 7–61 . March 1999 . 10049997 .
• King JE, Eugenin EA, Buckner CM, Berman JW . HIV tat and neurotoxicity . Microbes and Infection . 8 . 5 . 1347–1357 . April 2006 . 16697675 . 10.1016/j.micinf.2005.11.014 . free .
• Zimmer M, Fink TM, Franke Y, Lichter P, Spiess J . Cloning and structure of the gene encoding the human N-methyl-D-aspartate receptor (NMDAR1) . Gene . 159 . 2 . 219–223 . July 1995 . 7622053 . 10.1016/0378-1119(95)00044-7 .
• Karp SJ, Masu M, Eki T, Ozawa K, Nakanishi S . Molecular cloning and chromosomal localization of the key subunit of the human N-methyl-D-aspartate receptor . The Journal of Biological Chemistry . 268 . 5 . 3728–3733 . February 1993 . 7679115 . 10.1016/S0021-9258(18)53754-6 . free .
• Younkin DP, Tang CM, Hardy M, Reddy UR, Shi QY, Pleasure SJ, Lee VM, Pleasure D . 6 . Inducible expression of neuronal glutamate receptor channels in the NT2 human cell line . Proceedings of the National Academy of Sciences of the United States of America . 90 . 6 . 2174–2178 . March 1993 . 7681588 . 46048 . 10.1073/pnas.90.6.2174 . free . 1993PNAS...90.2174Y .
• Planells-Cases R, Sun W, Ferrer-Montiel AV, Montal M . Molecular cloning, functional expression, and pharmacological characterization of an N-methyl-D-aspartate receptor subunit from human brain . Proceedings of the National Academy of Sciences of the United States of America . 90 . 11 . 5057–5061 . June 1993 . 7685113 . 46653 . 10.1073/pnas.90.11.5057 . free . 1993PNAS...90.5057P .
• Magnuson DS, Knudsen BE, Geiger JD, Brownstone RM, Nath A . Human immunodeficiency virus type 1 tat activates non-N-methyl-D-aspartate excitatory amino acid receptors and causes neurotoxicity . Annals of Neurology . 37 . 3 . 373–380 . March 1995 . 7695237 . 10.1002/ana.410370314 . 24405132 .
• Foldes RL, Rampersad V, Kamboj RK . Cloning and sequence analysis of additional splice variants encoding human N-methyl-D-aspartate receptor (hNR1) subunits . Gene . 147 . 2 . 303–304 . September 1994 . 7926821 . 10.1016/0378-1119(94)90089-2 .
• Sheng M, Cummings J, Roldan LA, Jan YN, Jan LY . Changing subunit composition of heteromeric NMDA receptors during development of rat cortex . Nature . 368 . 6467 . 144–147 . March 1994 . 8139656 . 10.1038/368144a0 . 4332025 . 1994Natur.368..144S .
• Tingley WG, Roche KW, Thompson AK, Huganir RL . Regulation of NMDA receptor phosphorylation by alternative splicing of the C-terminal domain . Nature . 364 . 6432 . 70–73 . July 1993 . 8316301 . 10.1038/364070a0 . 4322831 . 1993Natur.364...70T .
• Foldes RL, Rampersad V, Kamboj RK . Cloning and sequence analysis of cDNAs encoding human hippocampus N-methyl-D-aspartate receptor subunits: evidence for alternative RNA splicing . Gene . 131 . 2 . 293–298 . September 1993 . 8406025 . 10.1016/0378-1119(93)90309-Q .
• Collins C, Duff C, Duncan AM, Planells-Cases R, Sun W, Norremolle A, Michaelis E, Montal M, Worton R, Hayden MR . 6 . Mapping of the human NMDA receptor subunit (NMDAR1) and the proposed NMDA receptor glutamate-binding subunit (NMDARA1) to chromosomes 9q34.3 and chromosome 8, respectively . Genomics . 17 . 1 . 237–239 . July 1993 . 8406459 . 10.1006/geno.1993.1311 .
• Lannuzel A, Lledo PM, Lamghitnia HO, Vincent JD, 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 . The European Journal of Neuroscience . 7 . 11 . 2285–2293 . November 1995 . 8563977 . 10.1111/j.1460-9568.1995.tb00649.x . 27201873 .
• Corasaniti MT, Melino G, Navarra M, Garaci E, Finazzi-Agrò A, Nisticò 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 . 4 . 3 . 315–321 . September 1995 . 8581564 . 10.1016/1055-8330(95)90021-7 .
• Ehlers MD, Zhang S, Bernhadt JP, Huganir RL . Inactivation of NMDA receptors by direct interaction of calmodulin with the NR1 subunit . Cell . 84 . 5 . 745–755 . March 1996 . 8625412 . 10.1016/S0092-8674(00)81052-1 . 1376853 . free .
• 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 . 10 . 5 . 463–468 . May 1996 . 8724036 . 10.1097/00002030-199605000-00003 . 1669986 .

Notes and References

1. Monyer H, Sprengel R, Schoepfer R, Herb A, Higuchi M, Lomeli H, Burnashev N, Sakmann B, Seeburg PH . 6 . Heteromeric NMDA receptors: molecular and functional distinction of subtypes . Science . 256 . 5060 . 1217–1221 . May 1992 . 1350383 . 10.1126/science.256.5060.1217 . 989677 . 1992Sci...256.1217M .
2. Web site: Entrez Gene: GRIN1 glutamate receptor, ionotropic, N-methyl D-aspartate 1.
3. Sengar AS, Li H, Zhang W, Leung C, Ramani AK, Saw NM, Wang Y, Tu Y, Ross PJ, Scherer SW, Ellis J, Brudno M, Jia Z, Salter MW . 6 . Control of Long-Term Synaptic Potentiation and Learning by Alternative Splicing of the NMDA Receptor Subunit GluN1 . Cell Reports . 29 . 13 . 4285–4294.e5 . December 2019 . 31875540 . 10.1016/j.celrep.2019.11.087 . 209482250 . free .
4. Liu H, Wang H, Peterson M, Zhang W, Hou G, Zhang ZW . N-terminal alternative splicing of GluN1 regulates the maturation of excitatory synapses and seizure susceptibility . Proceedings of the National Academy of Sciences of the United States of America . 116 . 42 . 21207–21212 . October 2019 . 31570583 . 6800312 . 10.1073/pnas.1905721116 . 2019PNAS..11621207L . free .
5. Herbrechter R, Hube N, Buchholz R, Reiner A . Splicing and editing of ionotropic glutamate receptors: a comprehensive analysis based on human RNA-Seq data . Cellular and Molecular Life Sciences . 78 . 14 . 5605–5630 . July 2021 . 34100982 . 8257547 . 10.1007/s00018-021-03865-z .
6. Manta G, Spathis AD, Taraviras S, Kouvelas ED, Mitsacos A . Age and visual experience-dependent expression of NMDAR1 splice variants in rat retina . Neurochemical Research . 36 . 8 . 1417–1425 . August 2011 . 21499738 . 10.1007/s11064-011-0467-5 . 11853676 .