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Gene Review

GRIA4  -  glutamate receptor, ionotropic, AMPA 4

Homo sapiens

Synonyms: AMPA-selective glutamate receptor 4, GLUR4, GLUR4C, GLURD, GluA4, ...
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Disease relevance of GRIA4


Psychiatry related information on GRIA4


High impact information on GRIA4

  • In order to identify key structural determinants for ligand recognition, we subjected the ligand-binding domain of the alpha-amino-3-hydroxy-5-methyl-4-isoxazole propionic acid (AMPA)-selective glutamate receptor GluR-D subunit to site-directed mutagenesis [6].
  • Glutamate stimulation of GluR4-containing AMPA receptors decreased cell viability, in a calcium-dependent manner, when the receptor desensitisation was prevented with cyclothiazide [7].
  • In this work, we investigated the downstream signals coupled to excitotoxicity mediated by Ca2+-permeable GluR4-containing AMPA receptors, using a HEK 293 cell line constitutively expressing the GluR4flip subunit of AMPA receptors (HEK-GluR4) [7].
  • The excitotoxic stimulation mediated through GluR4-containing AMPA receptors increased activator protein-1 (AP-1) DNA-binding activity [7].
  • Highly significant levels of mRNA were detected for the GluR1, GluR3, and GluR4 subunits [8].

Chemical compound and disease context of GRIA4


Biological context of GRIA4


Anatomical context of GRIA4


Associations of GRIA4 with chemical compounds

  • The hippocampi and adjacent temporal cortices of 24 human brains were examined with antibodies to the GluR1, GluR2/3, and GluR4 subunits of the D,L-alpha-amino-3-hydroxy-5-methyl-4-isoxazolepropionic acid-preferring glutamate receptor [15].
  • Protein kinase C gamma associates directly with the GluR4 alpha-amino-3-hydroxy-5-methyl-4-isoxazole propionate receptor subunit. Effect on receptor phosphorylation [18].
  • For optimal activity at hGluR4 receptors a 6-aza-substituted willardiine is favored [19].
  • Electrophysiological experiments also demonstrated that LY354740 also had no appreciable activity in cells expressing human recombinant AMPA (GluR4) and kainate (GluR6) receptors [20].
  • Whole-cell, voltage-clamp recordings from a human embryonic kidney cell line (HEK 293) stably expressing hGluR4 confirmed the presence of constitutively active, ligand-gated ion channels activated by AMPA, glutamate and kainate but not N-methyl-D-aspartate [14].

Physical interactions of GRIA4

  • Our results suggest that PKC gamma binds directly to GluR4, thereby modulating the function of GluR4-containing AMPA receptors [18].

Other interactions of GRIA4

  • Phosphorylation-dependent interactions of alpha-Actinin-1/IQGAP1 with the AMPA receptor subunit GluR4 [12].
  • In the cerebellum, GluR1 and GluR4 transcripts were expressed in the granular and Purkinje cell/Bergmann glia layers [21].
  • GluR3 and GluR4 mRNAs were expressed at very low levels [21].
  • The lethal combination of GluR2 and GluR4 subunits was found in high expression levels of both receptors [22].
  • Additionally, PKC gamma expression in GluR4 transfected human embryonic kidney 293T cells increased the amount of plasma membrane-associated GluR4 [18].

Analytical, diagnostic and therapeutic context of GRIA4


  1. 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]
  2. Localization of glutamate receptor subunits of the alpha-amino-3-hydroxy-5-methyl-4-isoxazolepropionate (AMPA) type in the pancreas of newborn guinea pigs. Liu, H.P., Tay, S.S., Leong, S.K. Pancreas (1997) [Pubmed]
  3. Excessive glutamate receptor 1 immunoreactivity in adult Down syndrome brains. Arai, Y., Mizuguchi, M., Takashima, S. Pediatric neurology. (1996) [Pubmed]
  4. A high-density microsatellite map of the ataxia-telangiectasia locus. Vanagaite, L., James, M.R., Rotman, G., Savitsky, K., Bar-Shira, A., Gilad, S., Ziv, Y., Uchenik, V., Sartiel, A., Collins, F.S. Hum. Genet. (1995) [Pubmed]
  5. In vitro eye-blink classical conditioning is NMDA receptor dependent and involves redistribution of AMPA receptor subunit GluR4. Keifer, J. J. Neurosci. (2001) [Pubmed]
  6. AMPA receptors and bacterial periplasmic amino acid-binding proteins share the ionic mechanism of ligand recognition. Lampinen, M., Pentikäinen, O., Johnson, M.S., Keinänen, K. EMBO J. (1998) [Pubmed]
  7. Excitotoxicity mediated by Ca2+-permeable GluR4-containing AMPA receptors involves the AP-1 transcription factor. Santos, A.E., Duarte, C.B., Iizuka, M., Barsoumian, E.L., Ham, J., Lopes, M.C., Carvalho, A.P., Carvalho, A.L. Cell Death Differ. (2006) [Pubmed]
  8. Calcium-permeable alpha-amino-3-hydroxy-5-methyl-4-isoxazole propionic acid receptors: a molecular determinant of selective vulnerability in amyotrophic lateral sclerosis. Williams, T.L., Day, N.C., Ince, P.G., Kamboj, R.K., Shaw, P.J. Ann. Neurol. (1997) [Pubmed]
  9. Targeting of GLUR4-containing AMPA receptors to synaptic sites during in vitro classical conditioning. Mokin, M., Keifer, J. Neuroscience (2004) [Pubmed]
  10. Abducens conditioning in in vitro turtle brain stem without cerebellum requires NMDA receptors and involves upregulation of GluR4-containing AMPA receptors. Keifer, J., Clark, T.G. Experimental brain research. Experimentelle Hirnforschung. Expérimentation cérébrale. (2003) [Pubmed]
  11. Positive association of the AMPA receptor subunit GluR4 gene (GRIA4) haplotype with schizophrenia: linkage disequilibrium mapping using SNPs evenly distributed across the gene region. Makino, C., Fujii, Y., Kikuta, R., Hirata, N., Tani, A., Shibata, A., Ninomiya, H., Tashiro, N., Shibata, H., Fukumaki, Y. Am. J. Med. Genet. B Neuropsychiatr. Genet. (2003) [Pubmed]
  12. Phosphorylation-dependent interactions of alpha-Actinin-1/IQGAP1 with the AMPA receptor subunit GluR4. Nuriya, M., Oh, S., Huganir, R.L. J. Neurochem. (2005) [Pubmed]
  13. GluR4c, an alternative splicing isoform of GluR4, is abundantly expressed in the adult human brain. Kawahara, Y., Ito, K., Sun, H., Ito, M., Kanazawa, I., Kwak, S. Brain Res. Mol. Brain Res. (2004) [Pubmed]
  14. Cloning, expression and pharmacological characterization of a human glutamate receptor: hGluR4. Fletcher, E.J., Nutt, S.L., Hoo, K.H., Elliott, C.E., Korczak, B., McWhinnie, E.A., Kamboj, R.K. Recept. Channels (1995) [Pubmed]
  15. Localization of non-N-methyl-D-aspartate glutamate receptors in normal and Alzheimer hippocampal formation. Hyman, B.T., Penney, J.B., Blackstone, C.D., Young, A.B. Ann. Neurol. (1994) [Pubmed]
  16. Flip and flop splice variants of AMPA receptor subunits in the spinal cord of amyotrophic lateral sclerosis. Tomiyama, M., Rodríguez-Puertas, R., Cortés, R., Pazos, A., Palacios, J.M., Mengod, G. Synapse (2002) [Pubmed]
  17. Distribution of AMPA receptor subunit mRNAs in the human basal ganglia: an in situ hybridization study. Tomiyama, M., Palacios, J.M., Cortés, R., Vilaró, M.T., Mengod, G. Brain Res. Mol. Brain Res. (1997) [Pubmed]
  18. Protein kinase C gamma associates directly with the GluR4 alpha-amino-3-hydroxy-5-methyl-4-isoxazole propionate receptor subunit. Effect on receptor phosphorylation. Correia, S.S., Duarte, C.B., Faro, C.J., Pires, E.V., Carvalho, A.L. J. Biol. Chem. (2003) [Pubmed]
  19. 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]
  20. LY354740 is a potent and highly selective group II metabotropic glutamate receptor agonist in cells expressing human glutamate receptors. Schoepp, D.D., Johnson, B.G., Wright, R.A., Salhoff, C.R., Mayne, N.G., Wu, S., Cockerman, S.L., Burnett, J.P., Belegaje, R., Bleakman, D., Monn, J.A. Neuropharmacology (1997) [Pubmed]
  21. Distribution of AMPA-selective glutamate receptor subunits in the human hippocampus and cerebellum. Day, N.C., Williams, T.L., Ince, P.G., Kamboj, R.K., Lodge, D., Shaw, P.J. Brain Res. Mol. Brain Res. (1995) [Pubmed]
  22. Stable expression of human homomeric and heteromeric AMPA receptor subunits in HEK293 cells. Nishimura, S., Iizuka, M., Wakamori, M., Akiba, I., Imoto, K., Barsoumian, E.L. Recept. Channels (2000) [Pubmed]
  23. Changes in glutamate receptor subunit composition in hippocampus and cortex in patients with refractory epilepsy. Grigorenko, E., Glazier, S., Bell, W., Tytell, M., Nosel, E., Pons, T., Deadwyler, S.A. J. Neurol. Sci. (1997) [Pubmed]
  24. Characterization of phosphorylation sites on the glutamate receptor 4 subunit of the AMPA receptors. Carvalho, A.L., Kameyama, K., Huganir, R.L. J. Neurosci. (1999) [Pubmed]
  25. Surface expression of GluR-D AMPA receptor is dependent on an interaction between its C-terminal domain and a 4.1 protein. Coleman, S.K., Cai, C., Mottershead, D.G., Haapalahti, J.P., Keinänen, K. J. Neurosci. (2003) [Pubmed]
  26. Selective synaptic distribution of AMPA and kainate receptor subunits in the outer plexiform layer of the carp retina. Schultz, K., Janssen-Bienhold, U., Weiler, R. J. Comp. Neurol. (2001) [Pubmed]
  27. Synaptic pattern of AMPA receptor subtypes upon direction-selective retinal ganglion cells. Jeong, S.A., Kwon, O.J., Lee, J.Y., Kim, T.J., Jeon, C.J. Neurosci. Res. (2006) [Pubmed]
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