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Gene Review

GRIA1  -  glutamate receptor, ionotropic, AMPA 1

Homo sapiens

Synonyms: AMPA-selective glutamate receptor 1, GLUH1, GLUR1, GLURA, GluA1, ...
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Disease relevance of GRIA1


Psychiatry related information on GRIA1


High impact information on GRIA1

  • In this study, we have shown a decrease in HIV-infected brain of the expression of mRNA and protein of the GluR-A flop subtype of alpha-amino-3-hydroxy-5-methyl-4-isoxazole propionic acid (AMPA) glutamate receptor in cerebellar Purkinje cells [10].
  • This effect was not diminished by mutating the CaMKII phosphorylation site on the GluR1 AMPA-R subunit, but was blocked by mutating a predicted PDZ domain interaction site [11].
  • These results show that LTP and CaMKII activity drive AMPA-Rs to synapses by a mechanism that requires the association between GluR1 and a PDZ domain protein [11].
  • Insertion of this exon cassette into the COOH-terminus of the GluR1 AMPA (alpha-amino-3-hydroxy-5-methyl-4-isoxazole propionate) receptor was sufficient to cause GluR1 to be localized to discrete, receptor-rich domains [12].
  • The steady-state current-voltage (I-V) relations of glutamate- and kainate-induced currents through homomeric channels fell into two classes: channels composed of either the GluR-A, -C, and -D subunits showed doubly rectifying I-V curves, and channels composed of the GluR-B subunits displayed simple outward rectification [13].

Chemical compound and disease context of GRIA1


Biological context of GRIA1


Anatomical context of GRIA1

  • In contrast, intense GluR1 labeling was observed in a small subpopulation of interneurons and low GluR1 immunoreactivity was present in many other cortical neurons [21].
  • The aim of the present study was to determine quantitatively GluR subunit combinations in the human temporal neocortex by double-labeling immunocyto- chemical experiments [1].
  • Results revealed statistically significant increases in the NAc, but not in the putamen, of NMDA receptor subunit (NR)1 and glutamate receptor subunit (GluR)2/3 wit trends in GluR1 and GluR5 in COD [22].
  • This study investigated whether the AMPA receptor subunit content (GluR1, GluR2, GluR2/3) within "vulnerable" vs. "resistant" sectors of the hippocampus is quantitatively altered with increasing AD neuropathology, as determined by Braak staging [23].
  • Motor neurons in the spinal cord, brainstem, and motor cortex were relatively strongly immunoreactive with the GluR2/3 subunit antibody, moderately so with the GluR4 subunit antibody, and showed relatively low levels of immunoreactivity with the GluR1 subunit antibody [24].

Associations of GRIA1 with chemical compounds

  • However, in rhesus monkeys chronically treated with antipsychotic drugs, clozapine treatment significantly decreased GRIA1 and increased GRIA3 mRNA expression, while both clozapine and haloperidol increased the expression of GRIA2 subunit mRNA [25].
  • We have characterized the phosphorylation of the glutamate receptor subunit GluR1, using biochemical and electrophysiological techniques [16].
  • It is suggested that the positive charge contributed by the arginine of the edited GluR-B(R) subunit determines low divalent permeability in heteromeric GluR channels and that changes in GluR-B(R) expression regulate the AMPA receptor-dependent divalent permeability of a cell [26].
  • Cyclic AMP-dependent protein kinase specifically phosphorylates SER-845 of GluR1 in transfected HEK cells and in neurons in culture [16].
  • These results indicate that clone HBGR1 codes for a glutamate receptor of the kainate subtype cognate to members of the glutamate receptor family from rodent brain [17].

Physical interactions of GRIA1

  • The present study was performed to elucidate whether SGK3 and stargazin interact or are effective through different pathways in the regulation of GluR1 [27].
  • This structure will predominate if GluR1 binds to GluR2 more rapidly during receptor assembly than other subunit combinations [28].
  • Crystal structure of the second PDZ domain of SAP97 in complex with a GluR-A C-terminal peptide [29].

Enzymatic interactions of GRIA1

  • Pretreatment with WAY-100635 counteracted the NBQX effects and restored the initial learning-specific increase in Ca2+/calmodulin-dependent protein kinase II (CaMKII) function and the later increase in GluR2/3 and phosphorylated GluR1 surface expression [30].
  • However, activity-dependent phosphorylation of substrates at synapses was highly selective in that the glutamate receptor subunits NR2B and GluR1 were poorly phosphorylated whereas PSD-95 and Stargazin, proteins implicated in the scaffolding and trafficking of AMPA receptors, were robustly phosphorylated [31].

Regulatory relationships of GRIA1

  • In conclusion, SGK3 and stargazin regulate GluR1 independently, and thus, their effects on glutamate-induced currents are additive [27].
  • The L-glutamate EC50 was 10.2 microM when wild-type GluR-A was coexpressed with GluR-B (GluR-A/B) and 38.9 microM when GluR-A445Q/B449Q receptors were tested [32].
  • The anesthetic 1-chloro-1,2,2-triflurocyclobutane (F3) weakly inhibited kainate responses in oocytes expressing GluR3 receptors but not oocytes expressing GluR1 or GluR2+3 receptors [33].
  • When CXCR2 was expressed with the AMPA-type glutamate receptor GluR1, CXCR2 dimerization was again impaired in a dose-dependent way, and receptor functions were prejudiced [34].
  • Stimulation of synaptic NMDA receptors by a protocol that induces chemical LTP resulted in a long-lasting reduction in the mobility of spine CaMKIIalpha and an increased mobile fraction but slower kinetics for spine GluR1 [35].

Other interactions of GRIA1

  • Fractional calcium currents through recombinant GluR channels of the NMDA, AMPA and kainate receptor subtypes [36].
  • We have investigated the subtype selectivity of these compounds by examining their binding affinity for homomeric hGluR1, -2, -4, or -5 (and hGluR6 in the case of 5-iodowillardiine (22)) [37].
  • 5-Fluorowillardiine (19) has higher affinity than AMPA for both homomeric hGluR1 and hGluR2 and compared to AMPA displays greater selectivity for AMPA receptor subtypes over the kainate receptor, hGluR5 [37].
  • Recovery from desensitization varied between 3.1 ms (GluR4 flip) and 178 ms (GluR1 flip) [38].
  • The prevalence of the NR2B subunit in thalamo-amygdaloid spines provides morphological evidence supporting its role in the fear conditioning circuit while the differential distribution of the GluR subtypes may reflect distinct roles for their involvement in this circuitry and synaptic plasticity [39].

Analytical, diagnostic and therapeutic context of GRIA1

  • The localization and expression of ionotropic non-N-methyl-D-aspartate glutamate receptors (GluR) were investigated in the developing and adult rat cerebellum using subunit-specific polyclonal antibodies for immunocytochemical, immunoblot and immunoprecipitation studies [40].
  • Presently, the kinetics of activation, desensitization and recovery from desensitization of human AMPARs (GluR1, 3 and 4 flip and flop, and GluR2 flip and flop in R and G edited forms, respectively) transiently expressed in HEK293 cells were studied with patch-clamp techniques and ultra fast agonist application [38].
  • We have quantitated the protein levels of alpha-amino-isoxazolepropionic acid (AMPA)-type (GluR1) and N-methyl-D-aspartate-type (NMDAR1) glutamate receptors in postmortem brain tissues of patients with Alzheimer's disease and age-matched controls using western blotting [41].
  • Gating was studied using ultra-fast drug perfusion of outside-out patches containing rat GluR-A or GluR6 subunits excised from transfected human embryonic kidney cells [42].
  • Interestingly, levels of a postsynaptic density protein named SAP97, which recognizes and potentially masks the epitope region of GluR1, was positively correlated with those of GluR1 protein in the control group, but not in the patient group [41].


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  10. Decreased expression of AMPA receptor messenger RNA and protein in AIDS: a model for HIV-associated neurotoxicity. Everall, I.P., Hudson, L., al-Sarraj, S., Honavar, M., Lantos, P., Kerwin, R. Nat. Med. (1995) [Pubmed]
  11. Driving AMPA receptors into synapses by LTP and CaMKII: requirement for GluR1 and PDZ domain interaction. Hayashi, Y., Shi, S.H., Esteban, J.A., Piccini, A., Poncer, J.C., Malinow, R. Science (2000) [Pubmed]
  12. Regulated subcellular distribution of the NR1 subunit of the NMDA receptor. Ehlers, M.D., Tingley, W.G., Huganir, R.L. Science (1995) [Pubmed]
  13. Structural determinants of ion flow through recombinant glutamate receptor channels. Verdoorn, T.A., Burnashev, N., Monyer, H., Seeburg, P.H., Sakmann, B. Science (1991) [Pubmed]
  14. AMPA/kainate receptor gene expression in normal and Alzheimer's disease hippocampus. Pellegrini-Giampietro, D.E., Bennett, M.V., Zukin, R.S. Neuroscience (1994) [Pubmed]
  15. Subthalamic stimulation-induced forelimb dyskinesias are linked to an increase in glutamate levels in the substantia nigra pars reticulata. Boulet, S., Lacombe, E., Carcenac, C., Feuerstein, C., Sgambato-Faure, V., Poupard, A., Savasta, M. J. Neurosci. (2006) [Pubmed]
  16. Characterization of multiple phosphorylation sites on the AMPA receptor GluR1 subunit. Roche, K.W., O'Brien, R.J., Mammen, A.L., Bernhardt, J., Huganir, R.L. Neuron (1996) [Pubmed]
  17. Molecular cloning, chromosomal mapping, and functional expression of human brain glutamate receptors. Sun, W., Ferrer-Montiel, A.V., Schinder, A.F., McPherson, J.P., Evans, G.A., Montal, M. Proc. Natl. Acad. Sci. U.S.A. (1992) [Pubmed]
  18. Chromosomal localization of human glutamate receptor genes. McNamara, J.O., Eubanks, J.H., McPherson, J.D., Wasmuth, J.J., Evans, G.A., Heinemann, S.F. J. Neurosci. (1992) [Pubmed]
  19. Dramatic increase of the RNA editing for glutamate receptor subunits during terminal differentiation of clonal human neurons. Lai, F., Chen, C.X., Lee, V.M., Nishikura, K. J. Neurochem. (1997) [Pubmed]
  20. Age-related changes in expression of AMPA-selective glutamate receptor subunits: is calcium-permeability altered in hippocampal neurons? Pagliusi, S.R., Gerrard, P., Abdallah, M., Talabot, D., Catsicas, S. Neuroscience (1994) [Pubmed]
  21. Quantitative localization of AMPA/kainate and kainate glutamate receptor subunit immunoreactivity in neurochemically identified subpopulations of neurons in the prefrontal cortex of the macaque monkey. Vickers, J.C., Huntley, G.W., Edwards, A.M., Moran, T., Rogers, S.W., Heinemann, S.F., Morrison, J.H. J. Neurosci. (1993) [Pubmed]
  22. Cocaine-induced alterations in nucleus accumbens ionotropic glutamate receptor subunits in human and non-human primates. Hemby, S.E., Tang, W., Muly, E.C., Kuhar, M.J., Howell, L., Mash, D.C. J. Neurochem. (2005) [Pubmed]
  23. Differential preservation of AMPA receptor subunits in the hippocampi of Alzheimer's disease patients according to Braak stage. Carter, T.L., Rissman, R.A., Mishizen-Eberz, A.J., Wolfe, B.B., Hamilton, R.L., Gandy, S., Armstrong, D.M. Exp. Neurol. (2004) [Pubmed]
  24. An immunocytochemical study of the distribution of AMPA selective glutamate receptor subunits in the normal human motor system. Williams, T.L., Ince, P.G., Oakley, A.E., Shaw, P.J. Neuroscience (1996) [Pubmed]
  25. AMPA receptor subunit and splice variant expression in the DLPFC of schizophrenic subjects and rhesus monkeys chronically administered antipsychotic drugs. O'connor, J.A., Muly, E.C., Arnold, S.E., Hemby, S.E. Schizophr. Res. (2007) [Pubmed]
  26. Divalent ion permeability of AMPA receptor channels is dominated by the edited form of a single subunit. Burnashev, N., Monyer, H., Seeburg, P.H., Sakmann, B. Neuron (1992) [Pubmed]
  27. Additive regulation of GluR1 by stargazin and serum- and glucocorticoid-inducible kinase isoform SGK3. Strutz-Seebohm, N., Seebohm, G., Korniychuk, G., Baltaev, R., Ureche, O., Striegel, M., Lang, F. Pflugers Arch. (2006) [Pubmed]
  28. Heteromeric AMPA receptors assemble with a preferred subunit stoichiometry and spatial arrangement. Mansour, M., Nagarajan, N., Nehring, R.B., Clements, J.D., Rosenmund, C. Neuron (2001) [Pubmed]
  29. Crystal structure of the second PDZ domain of SAP97 in complex with a GluR-A C-terminal peptide. von Ossowski, I., Oksanen, E., von Ossowski, L., Cai, C., Sundberg, M., Goldman, A., Kein??nen, K. FEBS J. (2006) [Pubmed]
  30. Opposing effects of AMPA and 5-HT1A receptor blockade on passive avoidance and object recognition performance: correlation with AMPA receptor subunit expression in rat hippocampus. Schiapparelli, L., Simón, A.M., Del Río, J., Frechilla, D. Neuropharmacology (2006) [Pubmed]
  31. Substrate Localization Creates Specificity in Calcium/Calmodulin-dependent Protein Kinase II Signaling at Synapses. Tsui, J., Malenka, R.C. J. Biol. Chem. (2006) [Pubmed]
  32. Functional effects of mutations in the putative agonist binding region of recombinant alpha-amino-3-hydroxy-5-methyl-4-isoxazolepropionic acid receptors. Li, F., Owens, N., Verdoorn, T.A. Mol. Pharmacol. (1995) [Pubmed]
  33. Anesthetics produce subunit-selective actions on glutamate receptors. Dildy-Mayfield, J.E., Eger, E.I., Harris, R.A. J. Pharmacol. Exp. Ther. (1996) [Pubmed]
  34. Ligand-independent CXCR2 dimerization. Trettel, F., Di Bartolomeo, S., Lauro, C., Catalano, M., Ciotti, M.T., Limatola, C. J. Biol. Chem. (2003) [Pubmed]
  35. Postsynaptic protein mobility in dendritic spines: long-term regulation by synaptic NMDA receptor activation. Sharma, K., Fong, D.K., Craig, A.M. Mol. Cell. Neurosci. (2006) [Pubmed]
  36. Fractional calcium currents through recombinant GluR channels of the NMDA, AMPA and kainate receptor subtypes. Burnashev, N., Zhou, Z., Neher, E., Sakmann, B. J. Physiol. (Lond.) (1995) [Pubmed]
  37. Synthesis of willardiine and 6-azawillardiine analogs: pharmacological characterization on cloned homomeric human AMPA and kainate receptor subtypes. Jane, D.E., Hoo, K., Kamboj, R., Deverill, M., Bleakman, D., Mandelzys, A. J. Med. Chem. (1997) [Pubmed]
  38. Kinetic properties of human AMPA-type glutamate receptors expressed in HEK293 cells. Grosskreutz, J., Zoerner, A., Schlesinger, F., Krampfl, K., Dengler, R., Bufler, J. Eur. J. Neurosci. (2003) [Pubmed]
  39. Distribution of NMDA and AMPA receptor subunits at thalamo-amygdaloid dendritic spines. Radley, J.J., Farb, C.R., He, Y., Janssen, W.G., Rodrigues, S.M., Johnson, L.R., Hof, P.R., Ledoux, J.E., Morrison, J.H. Brain Res. (2007) [Pubmed]
  40. Expression and heteromeric interactions of non-N-methyl-D-aspartate glutamate receptor subunits in the developing and adult cerebellum. Ripellino, J.A., Neve, R.L., Howe, J.R. Neuroscience (1998) [Pubmed]
  41. Phenotypic down-regulation of glutamate receptor subunit GluR1 in Alzheimer's disease. Wakabayashi, K., Narisawa-Saito, M., Iwakura, Y., Arai, T., Ikeda, K., Takahashi, H., Nawa, H. Neurobiol. Aging (1999) [Pubmed]
  42. External anions and cations distinguish between AMPA and kainate receptor gating mechanisms. Bowie, D. J. Physiol. (Lond.) (2002) [Pubmed]
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