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Gene Review

Gria1  -  glutamate receptor, ionotropic, AMPA1...

Mus musculus

Synonyms: 2900051M01Rik, AI853806, AMPA-selective glutamate receptor 1, Glr-1, Glr1, ...
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Disease relevance of Gria1

  • Significant reduction in glutamate receptor 1 (GluR1)- and GluR2/3-immunopositive neurons was demonstrated in the hilus of the dentate gyrus in mice killed on days 1, 7 and 60 after pilocarpine-induced status epilepticus (PISE) [1].
  • A reduction in the number of Ca(2+)-permeable AMPA receptors and density of AMPA channel currents in spinal neurons of GluR-A-deficient mice is accompanied by a loss of nociceptive plasticity in vitro and a reduction in acute inflammatory hyperalgesia in vivo [2].
  • The role of glutamate neurotoxicity in cerebral ischemia has long been advocated but still remains controversial, because various glutamate receptor (GluR) antagonists showed inconsistent protective efficacy in brain ischemia models [3].
  • The suppression in the later phase of retinal degeneration was specific to GluR1 and was not observed in GluR2-4 [4].
  • Threshold current intensities of the GluR epsilon 1 KO mice for wild running, clonic and tonic seizures were higher than those of wild-type mice [5].

Psychiatry related information on Gria1

  • GluR1-/- mice showed greater locomotor activity in a novel environment, but by the fifth day of repeated testing their activity was the same as that of wild-type mice [6].
  • In terms of alcohol drinking behavior, compared to wild-types, GluR1-/- mice differed neither in the acquisition of voluntary ethanol consumption nor in stress-induced ethanol drinking, nor in the expression of an alcohol deprivation effect (ADE) which is used as a model of relapse-like drinking behavior [6].
  • We studied the involvement of AMPA receptors in social interaction and anxiety and found that in several paradigms of agonistic behavior naïve male mice deficient for the GluR-A subunit- containing AMPA receptors are less aggressive than wild-type littermates [7].
  • Only in the GluR-A-/- mice did we observe reduced tolerance development in tail-flick antinociception and less severe naloxone-precipitated withdrawal symptoms after treatment with increasing morphine doses, without differences in plasma and brain morphine levels when compared with wild type [8].
  • Reduced cortical synaptic plasticity and GluR1 expression associated with fragile X mental retardation protein deficiency [9].

High impact information on Gria1

  • These results demonstrate that phosphorylation of GluR1 is critical for LTD and LTP expression and the retention of memories [10].
  • Of the six glutamate receptor (GluR) channel subunit families identified by molecular cloning, five have been shown to constitute either the AMPA, kainate, or NMDA receptor channel, whereas the function of the delta subunit family remains unknown [11].
  • We have used positional cloning to identify the mutations responsible for neurodegeneration in two independent Lc alleles as G-to-A transitions that change a highly conserved alanine to a threonine residue in transmembrane domain III of the mouse delta2 glutamate receptor gene (GluR delta2) [12].
  • Expression of the mutant GluR delta2(Lc) protein in Xenopus oocytes confirmed these results, demonstrating that Lc is inherited as a neurodegenerative disorder resulting from a gain-of-function mutation in a glutamate receptor gene [12].
  • Among GluR channel subtypes, the NMDA (N-methyl-D-aspartate) receptor channel which is highly permeable to Ca2+ is essential for the synaptic plasticity underlying memory, learning and development [13].

Chemical compound and disease context of Gria1


Biological context of Gria1

  • Consistent with this, both the extent of PKA phosphorylation on AMPAR subunit GluR1 and the expression of surface GluR1 are reduced in barrelless neurons [17].
  • However, no differences in alternative splicing of GluRs 1-3 were observed between young and old animals, suggesting that the fidelity of GluR transcript processing remains intact in the brains of aged animals [18].
  • Expression of the metabotropic glutamate receptor type 1 alpha (mGluR1 alpha) and the non-N-methyl-D-aspartate (NMDA) ionotropic glutamate receptor type 1 (GluR1) in mouse brain was investigated using the antibodies raised against the synthetic peptides corresponding to their C-terminal amino acid sequences [19].
  • These results suggest that a compositional change of AMPA receptor (increase of GluR1) and upregulation of the Bap31 gene may be implicated in fatigue in mice [20].
  • No change of gene expression of AMPA receptor subunits other than GluR1 was observed [20].

Anatomical context of Gria1

  • Distribution of flop/flip isoforms in the cortex, hippocampus, hypothalamus, and striatum varied between GluR subunits and brain region, with GluR2 showing the greatest differences [18].
  • Con-R was without effect on oocytes expressing the alpha-amino-3-hydroxy-5-methylisoxazole-4-propionic acid (AMPA) receptor subunit GluR1 or the kainate receptor subunit GluR6 [21].
  • In 9 of the 21 Frings mice exhibiting increased GluR1, but in none of the controls, bilateral structural lesions were observed in the lateral hypothalamus [22].
  • In the adult cerebellum, mGluR1 alpha is intensely expressed in Purkinje neurons and GluR1 in Bergmann glial cells [19].
  • Our results, firstly, support the idea that the expression of the GluRA subunit in Golgi epithelial cells may depend upon the sustained interaction with adjacent Purkinje cells, and secondly, suggest that granule cells which are more resistant to transsynaptic death may express higher levels of GluRB mRNA [23].

Associations of Gria1 with chemical compounds

  • The modulation of GluR1 agonist-initiated caspase-mediated cleavage by nicotine preconditioning offers a novel insight into how this agent can impart its numerous effects on the nervous system [24].
  • In agreement, we observed early reductions in surface expression of glutamate receptor subunit GluR1 in APP mutant neurons [25].
  • At a concentration of 10 microM, TB-3-4 had no effect on alpha-amino-3-hydroxy-5-methyl-4-isoxazolepropionic acid receptors expressed from the GluR1 subunit, indicating that TB-3-4 is a selective NMDA antagonist [26].
  • In addition, GluR1 and GluR2/3 immunostaining in the strata oriens, radiatum and lacunosum moleculare of areas CA1-3 decreased drastically on days 7 and 60 after PISE [1].
  • Homer, but not NR2A, mGlu5, and GluR1, was found to be less tyrosine phosphorylated in Fmr1 KO than control mice [27].

Physical interactions of Gria1


Enzymatic interactions of Gria1

  • Seven out of 25 tyrosine residues in the C-terminal cytoplasmic region of GluR epsilon 2 were phosphorylated by Fyn in vitro [30].
  • We found that AMPA receptor (AMPAR) glutamate receptor 1 (GluR1) subunits are persistently dephosphorylated in slices maintained in vitro for up to 8 h. alpha calcium/calmodulin-dependent kinase II (alphaCamKII) was also strongly dephosphorylated during the first 3 h in vitro but thereafter recovered to near control levels [31].

Co-localisations of Gria1

  • In primary hippocampal neurons, HIP1 colocalizes with GluR1-containing AMPA receptors and becomes concentrated in cell bodies following AMPA stimulation [32].

Regulatory relationships of Gria1


Other interactions of Gria1

  • However, gray matter neurons did express GluR1 and GluR2, as well as GluR2/3 [38].
  • We showed that mGluR1 alpha and GluR1 expression within the first 3 postnatal weeks undergoes dramatic changes in time and space, i.e., in the hippocampus and cerebellum [19].
  • Double immunofluorescence with the AMPA receptor GluRalpha1 (GluR1 or GluR-A) subunit further demonstrated that the GluRepsilon1 subunit was colocalized in a subset, not all, of GluRalpha1-immunopositive structures in the stratum lucidum [39].
  • Recently, the cytokine tumor necrosis factor-alpha (TNF-alpha) was shown to increase the cell surface expression of an AMPA receptor (AMPAR) subunit (GluR1) and to potentiate vulnerability to AMPAR-mediated injury [40].
  • The expressions of GluR1 and GluR2 also did not change, but the levels of polysialylated form of neuronal cell adhesion molecule (N-CAM) were reduced in the ORL1 receptor knockout as compared with wild-type mice [41].

Analytical, diagnostic and therapeutic context of Gria1


  1. Glutamate receptor 1-immunopositive neurons in the gliotic CA1 area of the mouse hippocampus after pilocarpine-induced status epilepticus. Tang, F.R., Chia, S.C., Zhang, S., Chen, P.M., Gao, H., Liu, C.P., Khanna, S., Lee, W.L. Eur. J. Neurosci. (2005) [Pubmed]
  2. The AMPA receptor subunits GluR-A and GluR-B reciprocally modulate spinal synaptic plasticity and inflammatory pain. Hartmann, B., Ahmadi, S., Heppenstall, P.A., Lewin, G.R., Schott, C., Borchardt, T., Seeburg, P.H., Zeilhofer, H.U., Sprengel, R., Kuner, R. Neuron (2004) [Pubmed]
  3. Attenuation of focal ischemic brain injury in mice deficient in the epsilon1 (NR2A) subunit of NMDA receptor. Morikawa, E., Mori, H., Kiyama, Y., Mishina, M., Asano, T., Kirino, T. J. Neurosci. (1998) [Pubmed]
  4. Effect of photoreceptor degeneration on RNA splicing and expression of AMPA receptors. Namekata, K., Okumura, A., Harada, C., Nakamura, K., Yoshida, H., Harada, T. Mol. Vis. (2006) [Pubmed]
  5. Mutation of NMDA receptor subunit epsilon 1: effects on audiogenic-like seizures induced by electrical stimulation of the inferior colliculus in mice. Sakamoto, T., Mishina, M., Niki, H. Brain Res. Mol. Brain Res. (2002) [Pubmed]
  6. Neurobehavioral effects of alcohol in AMPA receptor subunit (GluR1) deficient mice. Cowen, M.S., Schroff, K.C., Gass, P., Sprengel, R., Spanagel, R. Neuropharmacology (2003) [Pubmed]
  7. Reduced aggression in AMPA-type glutamate receptor GluR-A subunit-deficient mice. Vekovischeva, O.Y., Aitta-Aho, T., Echenko, O., Kankaanpää, A., Seppälä, T., Honkanen, A., Sprengel, R., Korpi, E.R. Genes Brain Behav. (2004) [Pubmed]
  8. Morphine-induced dependence and sensitization are altered in mice deficient in AMPA-type glutamate receptor-A subunits. Vekovischeva, O.Y., Zamanillo, D., Echenko, O., Seppälä, T., Uusi-Oukari, M., Honkanen, A., Seeburg, P.H., Sprengel, R., Korpi, E.R. J. Neurosci. (2001) [Pubmed]
  9. Reduced cortical synaptic plasticity and GluR1 expression associated with fragile X mental retardation protein deficiency. Li, J., Pelletier, M.R., Perez Velazquez, J.L., Carlen, P.L. Mol. Cell. Neurosci. (2002) [Pubmed]
  10. Phosphorylation of the AMPA receptor GluR1 subunit is required for synaptic plasticity and retention of spatial memory. Lee, H.K., Takamiya, K., Han, J.S., Man, H., Kim, C.H., Rumbaugh, G., Yu, S., Ding, L., He, C., Petralia, R.S., Wenthold, R.J., Gallagher, M., Huganir, R.L. Cell (2003) [Pubmed]
  11. Impairment of motor coordination, Purkinje cell synapse formation, and cerebellar long-term depression in GluR delta 2 mutant mice. Kashiwabuchi, N., Ikeda, K., Araki, K., Hirano, T., Shibuki, K., Takayama, C., Inoue, Y., Kutsuwada, T., Yagi, T., Kang, Y. Cell (1995) [Pubmed]
  12. Neurodegeneration in Lurcher mice caused by mutation in delta2 glutamate receptor gene. Zuo, J., De Jager, P.L., Takahashi, K.A., Jiang, W., Linden, D.J., Heintz, N. Nature (1997) [Pubmed]
  13. Functional characterization of a heteromeric NMDA receptor channel expressed from cloned cDNAs. Meguro, H., Mori, H., Araki, K., Kushiya, E., Kutsuwada, T., Yamazaki, M., Kumanishi, T., Arakawa, M., Sakimura, K., Mishina, M. Nature (1992) [Pubmed]
  14. In vivo recruitment by painful stimuli of AMPA receptor subunits to the plasma membrane of spinal cord neurons. Galan, A., Laird, J.M., Cervero, F. Pain (2004) [Pubmed]
  15. Ablation of the glucagon receptor gene increases fetal lethality and produces alterations in islet development and maturation. Vuguin, P.M., Kedees, M.H., Cui, L., Guz, Y., Gelling, R.W., Nejathaim, M., Charron, M.J., Teitelman, G. Endocrinology (2006) [Pubmed]
  16. Expression and characterization of the alpha 2 subunit of the alpha-amino-3-hydroxy-5-methyl-4-isoxazole propionate (AMPA)-selective glutamate receptor channel in a baculovirus system. Hattori, S., Okuda, K., Hamajima, K., Sakimura, K., Mishina, M., Kawamoto, S. Brain Res. (1994) [Pubmed]
  17. Adenylyl cyclase I regulates AMPA receptor trafficking during mouse cortical 'barrel' map development. Lu, H.C., She, W.C., Plas, D.T., Neumann, P.E., Janz, R., Crair, M.C. Nat. Neurosci. (2003) [Pubmed]
  18. RNA editing (Q/R site) and flop/flip splicing of AMPA receptor transcripts in young and old brains. Carlson, N.G., Howard, J., Gahring, L.C., Rogers, S.W. Neurobiol. Aging (2000) [Pubmed]
  19. Expression of the metabotropic glutamate receptor mGluR1 alpha and the ionotropic glutamate receptor GluR1 in the brain during the postnatal development of normal mouse and in the cerebellum from mutant mice. Ryo, Y., Miyawaki, A., Furuichi, T., Mikoshiba, K. J. Neurosci. Res. (1993) [Pubmed]
  20. Increase of AMPA receptor glutamate receptor 1 subunit and B-cell receptor-associated protein 31 gene expression in hippocampus of fatigued mice. Kamakura, M., Tamaki, K., Sakaki, T., Yoneda, Y. Neurosci. Lett. (2005) [Pubmed]
  21. In vitro and in vivo characterization of conantokin-R, a selective NMDA receptor antagonist isolated from the venom of the fish-hunting snail Conus radiatus. White, H.S., McCabe, R.T., Armstrong, H., Donevan, S.D., Cruz, L.J., Abogadie, F.C., Torres, J., Rivier, J.E., Paarmann, I., Hollmann, M., Olivera, B.M. J. Pharmacol. Exp. Ther. (2000) [Pubmed]
  22. Glutamate receptor GluR1 expression is altered selectively by chronic audiogenic seizures in the Frings mouse brain. Rogers, S.W., Gahring, L.C., White, H.S. J. Neurobiol. (1998) [Pubmed]
  23. AMPA receptor subunit RNA transcripts and [(3)H]AMPA binding in the cerebellum of normal and pcd mutant mice: an in situ hybridization study combined with receptor autoradiography. Fragioudaki, K., Giompres, P., Smith, A.L., Triarhou, L.C., Kouvelas, E.D., Mitsacos, A. Journal of neural transmission (Vienna, Austria : 1996) (2002) [Pubmed]
  24. Nicotine preconditioning antagonizes activity-dependent caspase proteolysis of a glutamate receptor. Meyer, E.L., Gahring, L.C., Rogers, S.W. J. Biol. Chem. (2002) [Pubmed]
  25. Beta-amyloid accumulation in APP mutant neurons reduces PSD-95 and GluR1 in synapses. Almeida, C.G., Tampellini, D., Takahashi, R.H., Greengard, P., Lin, M.T., Snyder, E.M., Gouras, G.K. Neurobiol. Dis. (2005) [Pubmed]
  26. Benzyl-polyamines: novel, potent N-methyl-D-aspartate receptor antagonists. Igarashi, K., Shirahata, A., Pahk, A.J., Kashiwagi, K., Williams, K. J. Pharmacol. Exp. Ther. (1997) [Pubmed]
  27. A reduced number of metabotropic glutamate subtype 5 receptors are associated with constitutive homer proteins in a mouse model of fragile X syndrome. Giuffrida, R., Musumeci, S., D'Antoni, S., Bonaccorso, C.M., Giuffrida-Stella, A.M., Oostra, B.A., Catania, M.V. J. Neurosci. (2005) [Pubmed]
  28. Novel blockade of protein kinase A-mediated phosphorylation of AMPA receptors. Vanhoose, A.M., Clements, J.M., Winder, D.G. J. Neurosci. (2006) [Pubmed]
  29. Direct interaction of post-synaptic density-95/Dlg/ZO-1 domain-containing synaptic molecule Shank3 with GluR1 alpha-amino-3-hydroxy-5-methyl-4-isoxazole propionic acid receptor. Uchino, S., Wada, H., Honda, S., Nakamura, Y., Ondo, Y., Uchiyama, T., Tsutsumi, M., Suzuki, E., Hirasawa, T., Kohsaka, S. J. Neurochem. (2006) [Pubmed]
  30. Characterization of Fyn-mediated tyrosine phosphorylation sites on GluR epsilon 2 (NR2B) subunit of the N-methyl-D-aspartate receptor. Nakazawa, T., Komai, S., Tezuka, T., Hisatsune, C., Umemori, H., Semba, K., Mishina, M., Manabe, T., Yamamoto, T. J. Biol. Chem. (2001) [Pubmed]
  31. Phosphorylation of proteins involved in activity-dependent forms of synaptic plasticity is altered in hippocampal slices maintained in vitro. Ho, O.H., Delgado, J.Y., O'Dell, T.J. J. Neurochem. (2004) [Pubmed]
  32. Disruption of the endocytic protein HIP1 results in neurological deficits and decreased AMPA receptor trafficking. Metzler, M., Li, B., Gan, L., Georgiou, J., Gutekunst, C.A., Wang, Y., Torre, E., Devon, R.S., Oh, R., Legendre-Guillemin, V., Rich, M., Alvarez, C., Gertsenstein, M., McPherson, P.S., Nagy, A., Wang, Y.T., Roder, J.C., Raymond, L.A., Hayden, M.R. EMBO J. (2003) [Pubmed]
  33. Tumor necrosis factor alpha increases neuronal vulnerability to excitotoxic necrosis by inducing expression of the AMPA-glutamate receptor subunit GluR1 via an acid sphingomyelinase- and NF-kappaB-dependent mechanism. Yu, Z., Cheng, G., Wen, X., Wu, G.D., Lee, W.T., Pleasure, D. Neurobiol. Dis. (2002) [Pubmed]
  34. Neurotensin regulates DARPP-32 thr34 phosphorylation in neostriatal neurons by activation of dopamine D1-type receptors. Matsuyama, S., Higashi, H., Maeda, H., Greengard, P., Nishi, A. J. Neurochem. (2002) [Pubmed]
  35. Altered intracellular localization of the glutamate receptor channel delta 2 subunit in weaver and reeler Purkinje cells. Takayama, C., Nakagawa, S., Watanabe, M., Kurihara, H., Mishina, M., Inoue, Y. Brain Res. (1997) [Pubmed]
  36. Identification of genes showing differential expression in anorexia mutant mouse. Chun, H.S., Park, Y., Yang, Y.K., Kim, d.o. .K., Son, J.H., Kim, S.J. Neuroreport (2003) [Pubmed]
  37. Regulation of phosphorylation of the GluR1 AMPA receptor in the neostriatum by dopamine and psychostimulants in vivo. Snyder, G.L., Allen, P.B., Fienberg, A.A., Valle, C.G., Huganir, R.L., Nairn, A.C., Greengard, P. J. Neurosci. (2000) [Pubmed]
  38. AMPA/kainate receptors in mouse spinal cord cell-specific display of receptor subunits by oligodendrocytes and astrocytes and at the nodes of Ranvier. Brand-Schieber, E., Werner, P. Glia (2003) [Pubmed]
  39. Selective scarcity of NMDA receptor channel subunits in the stratum lucidum (mossy fibre-recipient layer) of the mouse hippocampal CA3 subfield. Watanabe, M., Fukaya, M., Sakimura, K., Manabe, T., Mishina, M., Inoue, Y. Eur. J. Neurosci. (1998) [Pubmed]
  40. Tumor necrosis-factor-alpha (TNF-alpha) induces rapid insertion of Ca2+-permeable alpha-amino-3-hydroxyl-5-methyl-4-isoxazole-propionate (AMPA)/kainate (Ca-A/K) channels in a subset of hippocampal pyramidal neurons. Ogoshi, F., Yin, H.Z., Kuppumbatti, Y., Song, B., Amindari, S., Weiss, J.H. Exp. Neurol. (2005) [Pubmed]
  41. Neuronal mechanism of nociceptin-induced modulation of learning and memory: involvement of N-methyl-D-aspartate receptors. Mamiya, T., Yamada, K., Miyamoto, Y., König, N., Watanabe, Y., Noda, Y., Nabeshima, T. Mol. Psychiatry (2003) [Pubmed]
  42. Expression of AMPA and NMDA receptor subunits in the cervical spinal cord of wobbler mice. Bigini, P., Gardoni, F., Barbera, S., Cagnotto, A., Fumagalli, E., Longhi, A., Corsi, M.M., Di Luca, M., Mennini, T. BMC neuroscience (2006) [Pubmed]
  43. The Lurcher mutation of an alpha-amino-3-hydroxy-5-methyl- 4-isoxazolepropionic acid receptor subunit enhances potency of glutamate and converts an antagonist to an agonist. Taverna, F., Xiong, Z.G., Brandes, L., Roder, J.C., Salter, M.W., MacDonald, J.F. J. Biol. Chem. (2000) [Pubmed]
  44. NMDA receptors in cortical development are essential for the generation of coordinated increases in [Ca2+](i) in "neuronal domains". Okada, H., Miyakawa, N., Mori, H., Mishina, M., Miyamoto, Y., Hisatsune, T. Cereb. Cortex (2003) [Pubmed]
  45. Genetic mapping and evaluation of candidate genes for spasmodic, a neurological mouse mutation with abnormal startle response. Buckwalter, M.S., Testa, C.M., Noebels, J.L., Camper, S.A. Genomics (1993) [Pubmed]
  46. Immunohistochemical detection by immersion fixation with Carnoy solution of particular non-N-methyl-D-aspartate receptor subunits in murine hippocampus. Yoneyama, M., Kitayama, T., Taniura, H., Yoneda, Y. Neurochem. Int. (2004) [Pubmed]
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