The world's first wiki where authorship really matters (Nature Genetics, 2008). Due credit and reputation for authors. Imagine a global collaborative knowledge base for original thoughts. Search thousands of articles and collaborate with scientists around the globe.

wikigene or wiki gene protein drug chemical gene disease author authorship tracking collaborative publishing evolutionary knowledge reputation system wiki2.0 global collaboration genes proteins drugs chemicals diseases compound
Hoffmann, R. A wiki for the life sciences where authorship matters. Nature Genetics (2008)



Gene Review

Gria4  -  glutamate receptor, ionotropic, AMPA 4

Rattus norvegicus

Synonyms: AMPA-selective glutamate receptor 4, GluA4, GluR-4, GluR-D, GluR4, ...
Welcome! If you are familiar with the subject of this article, you can contribute to this open access knowledge base by deleting incorrect information, restructuring or completely rewriting any text. Read more.

Disease relevance of Gria4


High impact information on Gria4

  • Here we report the cloning and expression of a functional rat glutamate receptor subunit cDNA, GluR6, which has a very different pharmacology from that of the GluR1-GluR4 class [5].
  • When expressed in Xenopus oocytes the homomeric GluR6 receptor is activated by kainate, quisqualate and L-glutamate but not by AMPA, and the apparent affinity for kainate is higher than for receptors from the GluR1-GluR4 class [5].
  • Sequence homology between complementary DNA clones encoding non-NMDA glutamate receptor subunits reveals at least two subunit classes: the GluR1 to GluR4 class and the GluR5 class [5].
  • Cloned AMPA receptors carrying the "flop" splice variants of glutamate receptor subtype C (GluR-C) and GluR-D are shown to have desensitization time constants of around 1 millisecond, whereas those with the "flip" variants are about four times slower [6].
  • These findings suggest that rapid desensitization of AMPA receptors can be regulated by the expression and alternative splicing of GluR-D gene transcripts [6].

Biological context of Gria4

  • Screening a rat cerebellar cDNA library, we have now identified a third type of transcript derived from GluR-4 gene by differential RNA processing [7].
  • An intron within the 5'-untranslated region and Sp1, IK2 and E-box sites are conserved in the rat, mouse and human GluR4 promoters [1].
  • The rapid kinetics of GluR4-rich AMPA receptors we suggest indicate that cortical descending control may be more temporally precise than previously recognized [8].
  • GluR3-expressing glia appeared to be more susceptible to apoptosis than GluR4-expressing cells [9].
  • Activity-driven PKA phosphorylation of GluR4 was necessary and sufficient to relieve a retention interaction and drive receptors into synapses [10].

Anatomical context of Gria4


Associations of Gria4 with chemical compounds

  • In conclusion our results confirm the existence of glutamate ionotropic receptors of the AMPA type in primary astroglial cultures and suggest that GluR-4 is the main AMPA receptor subunit expressed in non-neuronal cells of the central nervous system [15].
  • Expression of AMPA receptor subunits (GluR1-GluR4) in gonadotrophin-releasing hormone neurones of young and middle-aged persistently oestrous rats during the steroid-induced luteinising hormone surge [16].
  • However, GluR3 mRNA was preferentially expressed by neurons coexpressing substance P and enkephalin and GluR4 mRNA was not detected in identified medium spiny neurons [17].
  • Deletion of the GluR4 transcriptional initiation region decreased luciferase activity in neurons, but increased activity in C6 cells, suggesting that regulatory elements governing neuronal expression reside in this region [1].
  • GluR4 mRNA levels did not differ between K10 and K25, although they were reduced by chronic exposure to NMDA [18].

Physical interactions of Gria4

  • Samples of paraventricular and lateral geniculate nuclei stained with GluR1 and of reticular nucleus as well as ventrobasal complex stained with GluR4 were used for the ultrastructural study [19].

Regulatory relationships of Gria4

  • GluR4 expression was maintained at higher levels at 08.00 and 12.00 h in young rats; although the percentage of Fos-positive GnRH neurones expressing GluR4 peaked at 12.00 h in young rats, it showed little change in MA-PE rats [16].
  • The nested PCR specific for GluR1-GluR4 showed that rat striatal NADPH-d(+) neurons expressed twice as much GluR1 mRNA as NADPH-d(-) neurons did [20].
  • During the following 2 weeks, GluR2/3 receptors were downregulated in exchange for GluR4 receptors [21].
  • Immunoreactivity for the GluR4 antibody was least abundant in the reticular formation and GluR4 immunoreactive cells were least likely to co-express calretinin [22].

Other interactions of Gria4

  • Granule cells, previously not known to receive glutamatergic input, expressed GluR2 and GluR4 subunits [11].
  • The data suggest that the composition of GluR1-GluR4 subunits on neurons in the cochlear nucleus may be related to presynaptic input; moreover, heterogeneous patterns of expression of the GluR3 subunit, in addition, suggest that variability in mRNA levels within one population of morphologically defined cells is present [11].
  • GluR4 immunoreactivity showed heavy staining in the external plexiform and olfactory nerve layers with localization to mitral cells, mitral/tufted dendritic processes, and olfactory nerve glial processes [23].
  • We have isolated cDNAs encoding a glutamate receptor subunit, designated GluR5, displaying 40%-41% amino acid identity with the kainate/AMPA receptor subunits GluR1, GluR2, GluR3, and GluR4 [24].
  • Half-lives were found to be 18 +/- 5 h and 23 +/- 8 h for the AMPA receptor subunits GluR2/3 and GluR4, respectively, and 16 +/- 5 h for NR2A [25].

Analytical, diagnostic and therapeutic context of Gria4

  • Under our experimental conditions employed, however, Western blotting assays failed to confirm the expression of receptor proteins for GluR1, GluR2/3 and GluR4 subunits in the adrenal cortex, adrenal medulla, adenohypophysis and neurohypophysis [26].
  • The following GluRs were cloned by isoform-specific RT-PCR from rat heart ribonucleic acid (RNA): GluR 1, GluR 3, GluR 4, GIuR 7, Ka 1, and Ka 2 [27].
  • Furthermore, in situ hybridization histochemistry revealed that the GluR-4c transcripts are preferentially expressed in cerebellar granule cells and Bergmann glial cells, whereas the expression of GluR-4 flip mRNAs is restricted to Bergmann glial cells [7].
  • Three transcripts of 6.2, 4.2, and 3.0 kilobases (kb) derived from the GluR-4 gene were identified on Northern blots containing total RNA prepared from different brain regions, using a cDNA probe or an oligonucleotide corresponding to the N-terminal region common to all transcripts [7].
  • Image analysis showed a significant decrease in the intensity of immunohistochemical labeling for the GluR2/3 and GluR4 subunits in motoneurons, although most motoneurons were still immunopositive for these 2 subunits after axotomy [28].


  1. Activity of the rat GluR4 promoter in transfected cortical neurons and glia. Borges, K., Myers, S.J., Zhang, S., Dingledine, R. J. Neurochem. (2003) [Pubmed]
  2. Cellular distributions of AMPA glutamate receptor subunits in fetal ventral mesencephalon transplants in the dopamine-depleted striatum of a rat. Todaka, K., Ishida, Y., Kuwahara, I., Nishimori, T., Mitsuyama, Y. Brain Res. Bull. (1998) [Pubmed]
  3. Expression of ionotropic glutamate receptor subunits in glial cells of the hippocampal CA1 area following transient forebrain ischemia. Gottlieb, M., Matute, C. J. Cereb. Blood Flow Metab. (1997) [Pubmed]
  4. Cellular and subcellular localization of AMPA-selective glutamate receptors in the mammalian peripheral vestibular system. Demêmes, D., Lleixa, A., Dechesne, C.J. Brain Res. (1995) [Pubmed]
  5. Cloning of a cDNA for a glutamate receptor subunit activated by kainate but not AMPA. Egebjerg, J., Bettler, B., Hermans-Borgmeyer, I., Heinemann, S. Nature (1991) [Pubmed]
  6. A molecular determinant for submillisecond desensitization in glutamate receptors. Mosbacher, J., Schoepfer, R., Monyer, H., Burnashev, N., Seeburg, P.H., Ruppersberg, J.P. Science (1994) [Pubmed]
  7. Molecular cloning and development analysis of a new glutamate receptor subunit isoform in cerebellum. Gallo, V., Upson, L.M., Hayes, W.P., Vyklicky, L., Winters, C.A., Buonanno, A. J. Neurosci. (1992) [Pubmed]
  8. Differential synaptic distribution of AMPA receptor subunits in the ventral posterior and reticular thalamic nuclei of the rat. Mineff, E.M., Weinberg, R.J. Neuroscience (2000) [Pubmed]
  9. Changes in glial cell white matter AMPA receptor expression after spinal cord injury and relationship to apoptotic cell death. Park, E., Liu, Y., Fehlings, M.G. Exp. Neurol. (2003) [Pubmed]
  10. PKA phosphorylation of AMPA receptor subunits controls synaptic trafficking underlying plasticity. Esteban, J.A., Shi, S.H., Wilson, C., Nuriya, M., Huganir, R.L., Malinow, R. Nat. Neurosci. (2003) [Pubmed]
  11. Expression of AMPA-selective glutamate receptor subunits in morphologically defined neurons of the mammalian cochlear nucleus. Hunter, C., Petralia, R.S., Vu, T., Wenthold, R.J. J. Neurosci. (1993) [Pubmed]
  12. AMPA glutamate receptor subunits are differentially distributed in rat brain. Martin, L.J., Blackstone, C.D., Levey, A.I., Huganir, R.L., Price, D.L. Neuroscience (1993) [Pubmed]
  13. AMPA receptors in the rat and primate hippocampus: a possible absence of GluR2/3 subunits in most interneurons. Leranth, C., Szeidemann, Z., Hsu, M., Buzsáki, G. Neuroscience (1996) [Pubmed]
  14. Distribution of non-NMDA glutamate receptor mRNAs in the developing rat cochlea. Luo, L., Brumm, D., Ryan, A.F. J. Comp. Neurol. (1995) [Pubmed]
  15. AMPA-selective glutamate receptor subunits in astroglial cultures. Condorelli, D.F., Dell'Albani, P., Corsaro, M., Barresi, V., Giuffrida Stella, A.M. J. Neurosci. Res. (1993) [Pubmed]
  16. Expression of AMPA receptor subunits (GluR1-GluR4) in gonadotrophin-releasing hormone neurones of young and middle-aged persistently oestrous rats during the steroid-induced luteinising hormone surge. Bailey, J.D., Centers, A., Jennes, L. J. Neuroendocrinol. (2006) [Pubmed]
  17. Physiological and molecular properties of AMPA/Kainate receptors expressed by striatal medium spiny neurons. Stefani, A., Chen, Q., Flores-Hernandez, J., Jiao, Y., Reiner, A., Surmeier, D.J. Dev. Neurosci. (1998) [Pubmed]
  18. Growth conditions differentially regulate the expression of alpha-amino-3-hydroxy-5-methylisoxazole-4-propionate (AMPA) receptor subunits in cultured neurons. Condorelli, D.F., Dell'Albani, P., Aronica, E., Genazzani, A.A., Casabona, G., Corsaro, M., Balázs, R., Nicoletti, F. J. Neurochem. (1993) [Pubmed]
  19. Distribution of AMPA selective glutamate receptors in the thalamus of adult rats and during postnatal development. A light and ultrastructural immunocytochemical study. Spreafico, R., Frassoni, C., Arcelli, P., Battaglia, G., Wenthold, R.J., De Biasi, S. Brain Res. Dev. Brain Res. (1994) [Pubmed]
  20. High abundance of GluR1 mRNA and reduced Q/R editing of GluR2 mRNA in individual NADPH-diaphorase neurons. Kim, D.Y., Kim, S.H., Choi, H.B., Min , C., Gwag, B.J. Mol. Cell. Neurosci. (2001) [Pubmed]
  21. Transient expression of NMDA receptors during rearrangement of AMPA-receptor-expressing fibers in the developing inner ear. Knipper, M., Köpschall, I., Rohbock, K., Köpke, A.K., Bonk, I., Zimmermann, U., Zenner, H. Cell Tissue Res. (1997) [Pubmed]
  22. Calretinin mRNA and immunoreactivity in the medullary reticular formation of the rat: colocalization with glutamate receptors. Winsky, L., Isaacs, K.R., Jacobowitz, D.M. Brain Res. (1996) [Pubmed]
  23. Differential distribution of ionotropic glutamate receptor subunits in the rat olfactory bulb. Montague, A.A., Greer, C.A. J. Comp. Neurol. (1999) [Pubmed]
  24. Cloning of a novel glutamate receptor subunit, GluR5: expression in the nervous system during development. Bettler, B., Boulter, J., Hermans-Borgmeyer, I., O'Shea-Greenfield, A., Deneris, E.S., Moll, C., Borgmeyer, U., Hollmann, M., Heinemann, S. Neuron (1990) [Pubmed]
  25. Turnover analysis of glutamate receptors identifies a rapidly degraded pool of the N-methyl-D-aspartate receptor subunit, NR1, in cultured cerebellar granule cells. Huh, K.H., Wenthold, R.J. J. Biol. Chem. (1999) [Pubmed]
  26. Expression of GluR6/7 subunits of kainate receptors in rat adenohypophysis. Hinoi, E., Yoneda, Y. Neurochem. Int. (2001) [Pubmed]
  27. Molecular and immunochemical characterization of the ionotropic glutamate receptors in the rat heart. Gill, S.S., Pulido, O.M., Mueller, R.W., McGuire, P.F. Brain Res. Bull. (1998) [Pubmed]
  28. Ionotropic glutamate receptor subunits are differentially regulated in the motoneuronal pools of the rat hypoglossal nucleus in response to axotomy. García Del Caño, G., Gerrikagoitia, I., Sarasa, M., Matute, C., Martínez-Millán, L. J. Neurocytol. (2000) [Pubmed]
WikiGenes - Universities