GRIA1 explained

Glutamate receptor 1 is a protein that in humans is encoded by the GRIA1 gene.^{[1] [2]}

Function

Glutamate receptors are the predominant excitatory neurotransmitter receptors in the mammalian brain and are activated in a variety of normal neurophysiologic processes. These receptors are heteromeric protein complexes with multiple subunits, each possessing transmembrane regions, and all arranged to form a ligand-gated ion channel. The classification of glutamate receptors is based on their activation by different pharmacologic agonists. The GRIA1 belongs to a family of alpha-amino-3-hydroxy-5-methyl-4-isoxazole propionate (AMPA) receptors. Each of the members (GRIA1–4) include flip and flop isoforms generated by alternative RNA splicing. The receptor subunits encoded by each isoform vary in their signal transduction properties. The isoform presented here is the flop isoform. In situ hybridization experiments showed that human GRIA1 mRNA is present in granule and pyramidal cells in the hippocampal formation.^[3]

GRIA1 (GluR1) is centrally involved in synaptic plasticity. Expression of the GluR1 gene is significantly reduced in the human frontal cortex with increasing age.^[4]

Interactions

GRIA1 has been shown to interact with:

• DLG1^{[5] [6] [7]}
• EPB41L2,^[8] and
• GRID2.^[9]

See also

• AMPA receptor

Further reading

• Sun W, Ferrer-Montiel AV, Schinder AF, McPherson JP, Evans GA, Montal M . Molecular cloning, chromosomal mapping, and functional expression of human brain glutamate receptors. . Proc. Natl. Acad. Sci. U.S.A. . 89 . 4 . 1443–1447 . 1992 . 1311100 . 48467 . 10.1073/pnas.89.4.1443 . 1992PNAS...89.1443S . free .
• Potier MC, Spillantini MG, Carter NP . The human glutamate receptor cDNA GluR1: cloning, sequencing, expression and localization to chromosome 5. . DNA Seq. . 2 . 4 . 211–218 . 1992 . 1320959 . 10.3109/10425179209020805 .
• Yakel JL, Vissavajjhala P, Derkach VA, Brickey DA, Soderling TR . Identification of a Ca2+/calmodulin-dependent protein kinase II regulatory phosphorylation site in non-N-methyl-D-aspartate glutamate receptors. . Proc. Natl. Acad. Sci. U.S.A. . 92 . 5 . 1376–1380 . 1995 . 7877986 . 42522 . 10.1073/pnas.92.5.1376 . 1995PNAS...92.1376Y . free .
• Eastwood SL, Burnet PW, Beckwith J, Kerwin RW, Harrison PJ . AMPA glutamate receptors and their flip and flop mRNAs in human hippocampus. . NeuroReport . 5 . 11 . 1325–1328 . 1994 . 7919190 . 10.1097/00001756-199406270-00007 .
• Roche KW, Raymond LA, Blackstone C, Huganir RL . Transmembrane topology of the glutamate receptor subunit GluR6. . J. Biol. Chem. . 269 . 16 . 11679–11682 . 1994 . 10.1016/S0021-9258(17)32623-6 . 8163463 . free .
• McLaughlin DP, Cheetham ME, Kerwin RW . Expression of alternatively-spliced glutamate receptors in human hippocampus. . Eur. J. Pharmacol. . 244 . 1 . 89–92 . 1993 . 8420792 . 10.1016/0922-4106(93)90062-E .
• Roche KW, O'Brien RJ, Mammen AL, Bernhardt J, Huganir RL . Characterization of multiple phosphorylation sites on the AMPA receptor GluR1 subunit. . Neuron . 16 . 6 . 1179–1188 . 1996 . 8663994 . 10.1016/S0896-6273(00)80144-0 . 18608781 . free .
• Brakeman PR, Lanahan AA, O'Brien R, Roche K, Barnes CA, Huganir RL, Worley PF . Homer: a protein that selectively binds metabotropic glutamate receptors. . Nature . 386 . 6622 . 284–288 . 1997 . 9069287 . 10.1038/386284a0 . 1997Natur.386..284B . 4346579 .
• Barria A, Derkach V, Soderling T . Identification of the Ca2+/calmodulin-dependent protein kinase II regulatory phosphorylation site in the alpha-amino-3-hydroxyl-5-methyl-4-isoxazole-propionate-type glutamate receptor. . J. Biol. Chem. . 272 . 52 . 32727–32730 . 1998 . 9407043 . 10.1074/jbc.272.52.32727 . free .
• Ripellino JA, Neve RL, Howe JR . Expression and heteromeric interactions of non-N-methyl-D-aspartate glutamate receptor subunits in the developing and adult cerebellum. . Neuroscience . 82 . 2 . 485–497 . 1998 . 9466455 . 10.1016/S0306-4522(97)00296-0 . 23219004 . free .
• Leonard AS, Davare MA, Horne MC, Garner CC, Hell JW . SAP97 is associated with the alpha-amino-3-hydroxy-5-methylisoxazole-4-propionic acid receptor GluR1 subunit. . J. Biol. Chem. . 273 . 31 . 19518–19524 . 1998 . 9677374 . 10.1074/jbc.273.31.19518 . free .
• Xiao B, Tu JC, Petralia RS, Yuan JP, Doan A, Breder CD, Ruggiero A, Lanahan AA, Wenthold RJ, Worley PF . Homer regulates the association of group 1 metabotropic glutamate receptors with multivalent complexes of homer-related, synaptic proteins. . Neuron . 21 . 4 . 707–716 . 1998 . 9808458 . 10.1016/S0896-6273(00)80588-7 . 16431031 . free .
• Montague AA, Greer CA . Differential distribution of ionotropic glutamate receptor subunits in the rat olfactory bulb. . J. Comp. Neurol. . 405 . 2 . 233–246 . 1999 . 10023812 . 10.1002/(SICI)1096-9861(19990308)405:2<233::AID-CNE7>3.0.CO;2-A . 1317987 .
• Leuschner WD, Hoch W . Subtype-specific assembly of alpha-amino-3-hydroxy-5-methyl-4-isoxazole propionic acid receptor subunits is mediated by their n-terminal domains. . J. Biol. Chem. . 274 . 24 . 16907–16916 . 1999 . 10358037 . 10.1074/jbc.274.24.16907 . free .
• Karel Svoboda (scientist) . Shi SH, Hayashi Y, Petralia RS, Zaman SH, Wenthold RJ, Svoboda K, Malinow R . Rapid spine delivery and redistribution of AMPA receptors after synaptic NMDA receptor activation. . Science . 284 . 5421 . 1811–1816 . 1999 . 10364548 . 10.1126/science.284.5421.1811 . 10.1.1.376.3281 .
• Rubio ME, Wenthold RJ . Calnexin and the immunoglobulin binding protein (BiP) coimmunoprecipitate with AMPA receptors. . J. Neurochem. . 73 . 3 . 942–948 . 1999 . 10461883 . 10.1046/j.1471-4159.1999.0730942.x . 25957729 . free .
• Stinehelfer S, Vruwink M, Burette A . Immunolocalization of mGluR1alpha in specific populations of local circuit neurons in the cerebral cortex. . Brain Res. . 861 . 1 . 37–44 . 2000 . 10751563 . 10.1016/S0006-8993(00)01952-1 . 38665483 .

Notes and References

1. Puckett C, Gomez CM, Korenberg JR, Tung H, Meier TJ, Chen XN, Hood L . Molecular cloning and chromosomal localization of one of the human glutamate receptor genes . Proc Natl Acad Sci U S A . 88 . 17 . 7557–7561 . October 1991 . 1652753 . 52340 . 10.1073/pnas.88.17.7557 . 1991PNAS...88.7557P . free .
2. McNamara JO, Eubanks JH, McPherson JD, Wasmuth JJ, Evans GA, Heinemann SF . Chromosomal localization of human glutamate receptor genes . J Neurosci . 12 . 7 . 2555–2562 . July 1992 . 1319477 . 6575855. 10.1523/JNEUROSCI.12-07-02555.1992. free .
3. Web site: Entrez Gene: GRIA1 glutamate receptor, ionotropic, AMPA 1.
4. Lu T, Pan Y, Kao SY, Li C, Kohane I, Chan J, Yankner BA . Gene regulation and DNA damage in the ageing human brain . Nature . 429 . 6994 . 883–891 . June 2004 . 15190254 . 10.1038/nature02661 . 2004Natur.429..883L . 1867993 .
5. Gardoni F, Mauceri D, Fiorentini C, Bellone C, Missale C, Cattabeni F, Di Luca M . CaMKII-dependent phosphorylation regulates SAP97/NR2A interaction . J. Biol. Chem. . 278 . 45 . 44745–44752 . November 2003 . 12933808 . 10.1074/jbc.M303576200 . free .
6. Leonard AS, Davare MA, Horne MC, Garner CC, Hell JW . SAP97 is associated with the alpha-amino-3-hydroxy-5-methylisoxazole-4-propionic acid receptor GluR1 subunit . J. Biol. Chem. . 273 . 31 . 19518–19524 . July 1998 . 9677374 . 10.1074/jbc.273.31.19518. free .
7. Sans N, Racca C, Petralia RS, Wang YX, McCallum J, Wenthold RJ . Synapse-associated protein 97 selectively associates with a subset of AMPA receptors early in their biosynthetic pathway . J. Neurosci. . 21 . 19 . 7506–7516 . October 2001 . 11567040 . 10.1523/JNEUROSCI.21-19-07506.2001. 6762903 . free .
8. Shen L, Liang F, Walensky LD, Huganir RL . Regulation of AMPA receptor GluR1 subunit surface expression by a 4. 1N-linked actin cytoskeletal association . J. Neurosci. . 20 . 21 . 7932–7940 . November 2000 . 11050113 . 10.1523/JNEUROSCI.20-21-07932.2000. 6772741 . free .
9. Kohda K, Kamiya Y, Matsuda S, Kato K, Umemori H, Yuzaki M . Heteromer formation of delta2 glutamate receptors with AMPA or kainate receptors . Brain Res. Mol. Brain Res. . 110 . 1 . 27–37 . January 2003 . 12573530 . 10.1016/s0169-328x(02)00561-2.