Alternative titles; symbols
HGNC Approved Gene Symbol: GRIK1
Cytogenetic location: 21q21.3 Genomic coordinates (GRCh38) : 21:29,536,933-29,939,996 (from NCBI)
Eubanks et al. (1993) isolated genomic clones of the human non-N-methyl-D-aspartate (non-NMDA) glutamate receptor subunit GLUR5 by high-stringency screening of a cosmid library using the rat cDNA as a probe. GLUR5 transcripts are expressed in the ventral horn of the spinal cord, the region in which motor neurons reside. Comparing 2 isoforms of GLUR5, GluR5-1d and EAA3a, Barbon and Barlati (2000) found that they share a common N-terminal portion, show completely different C-termini sequences, and differ by 15 amino acids, which are present in GluR5-1d and absent in EAA3a, in the central part of the protein. Barbon and Barlati (2000) postulated the existence of other isoforms of GluR5 mRNA, given the presence of multiple splicing sites.
Barbon and Barlati (2000) used sequence data available from public databases to determine that the GLUR5 gene has 18 exons and spans approximately 400 kb.
By Southern hybridization of DNAs isolated from mapping panels of Chinese hamster-human hybrid cell lines and by high-resolution in situ suppression hybridization, Eubanks et al. (1993) localized the GLUR5 gene to 21q21.1-q22.1. Potier et al. (1993) showed that GLUR5 maps to 21q22 by screening a chromosome 21 YAC library. Using a tetranucleotide AGAT repeat for linkage analysis, Gregor et al. (1994) placed the GLUR5 gene 5 cM telomeric to APP (104760) and 3 cM centromeric to SOD1 (147450).
Gregor et al. (1992, 1993) reported the location of GLUR5 on 21q21-q22.1 and cited evidence that GLUR5 was a candidate gene for ALS. However, in an addendum, Gregor et al. (1993) reported that 2 recombinations had occurred in segregation analyses of polymorphic GLUR5 markers in families with chromosome 21-linked ALS, thus excluding GLUR5 as a candidate gene for this disorder.
Using PCR with a panel of DNA from an interspecific backcross, and through RFLV and haplotype analyses, Gregor et al. (1993) mapped the Glur5 gene in the mouse to chromosome 16 between App and Sod1.
The structure and function of glutamate receptor subunits GLUR2 (138247), GLUR5, and GLUR6 (138244) are changed by RNA editing, changing the triplet CAG (coding for glutamine) to CGG (coding for arginine). Paschen and Djuricic (1994) studied the extent of RNA editing of GLUR5 in different brain regions of control rats, based on a restriction analysis of PCR products from reverse-transcribed mRNA. The extent of RNA editing of GLUR5 varied among different brain regions, ranging from 41% in the white matter to 91% in the thalamus. The authors proposed that RNA editing of glutamate receptor subunits may be important in controlling the rate of calcium flux through non-NMDA receptor channels in different physiologic or pathologic states of the brain.
Ouardouz et al. (2009) demonstrated that myelinated axons from rat spinal cord express functional GluR5-containing kainate receptors capable of mediating a deleterious increase in intraaxonal calcium, resulting in axonal degeneration and white matter injury. The GluR5-mediated calcium increase was mediated by both ionotropic and noncanonic signaling. Immunohistochemical studies showed GluR5 and GluR4 (GRIA4; 138246) clustered at the surface of myelinated axons; GluR5 coimmunoprecipitated with Nos1 (163731) and colocalized with Nos1 clusters on the internodal axon. In addition, the GluR5 response was reduced by intraaxonal nitric oxide scavengers, suggesting a functional association between GluR5 and Nos1.
For discussion of a possible association between variation in the GRIK1 gene and susceptibility to juvenile absence epilepsy, see EJA1 (607631).
Kainate receptors alter the excitability of mossy fiber axons and have been reported to play a role in the induction of long-term potentiation (LTP) at mossy fiber synapses in the hippocampus. Contractor et al. (2001) investigated short- and long-term facilitation of mossy fiber synaptic transmission in kainate receptor knockout mice. Contractor et al. (2001) found that LTP was reduced in mice lacking the GLUR6, but not the GLUR5, kainate receptor subunit. Additionally, short-term synaptic facilitation was impaired in Glur6 knockout mice, suggesting that kainate receptors act as presynaptic autoreceptors on mossy fiber terminals to facilitate synaptic transmission. Contractor et al. (2001) concluded that their data demonstrate that kainate receptors containing the GLUR6 subunit are important modulators of mossy fiber synaptic strength.
Using the muscarinic agonist pilocarpine to induce epileptiform activity in hippocampal slices and limbic seizures in rats, Smolders et al. (2002) showed that GLUR5 antagonists prevented and interrupted seizure activity without overt side effects. The authors suggested a role for these compounds in the treatment of human temporal lobe epilepsy.
Barbon, A., Barlati, S. Genomic organization, proposed alternative splicing mechanisms, and RNA editing structure of GRIK1. Cytogenet. Cell Genet. 88: 236-239, 2000. [PubMed: 10828597] [Full Text: https://doi.org/10.1159/000015558]
Contractor, A., Swanson, G., Heinemann, S. F. Kainate receptors are involved in short- and long-term plasticity at mossy fiber synapses in the hippocampus. Neuron 29: 209-216, 2001. [PubMed: 11182092] [Full Text: https://doi.org/10.1016/s0896-6273(01)00191-x]
Eubanks, J. H., Puranam, R. S., Kleckner, N. W., Bettler, B., Heinemann, S. F., McNamara, J. O. The gene encoding the glutamate receptor subunit GluR5 is located on human chromosome 21q21.1-22.1 in the vicinity of the gene for familial amyotrophic lateral sclerosis. Proc. Nat. Acad. Sci. 90: 178-182, 1993. [PubMed: 8419920] [Full Text: https://doi.org/10.1073/pnas.90.1.178]
Gregor, P., Gaston, S. M., Yang, X., O'Regan, J. P., Rosen, D. R., Tanzi, R. E., Patterson, D., Haines, J. L., Horvitz, H. R., Uhl, G. R., Brown, R. H., Jr. Genetic and physical mapping of the GLUR5 glutamate receptor gene on human chromosome 21. Hum. Genet. 94: 565-570, 1994. [PubMed: 7959697] [Full Text: https://doi.org/10.1007/BF00211029]
Gregor, P., Reeves, R. H., Jabs, E. W., Yang, X., Dackowski, W., Rochelle, J. M., Brown, R. H., Jr., Haines, J. L., O'Hara, B. F., Uhl, G. R., Seldin, M. F. Chromosomal localization of glutamate receptor genes: relationship to familial amyotrophic lateral sclerosis and other neurological disorders of mice and humans. Proc. Nat. Acad. Sci. 90: 3053-3057, 1993. [PubMed: 8464923] [Full Text: https://doi.org/10.1073/pnas.90.7.3053]
Gregor, P., Seldin, M. F., Reevess, R., Jabs, E., Yang, X., Rochelle, J. M., O'Hara, B. F., Uhl, G. R. Chromosomal localization of glutamate receptor genes: candidates for familial amyotrophic lateral sclerosis and other neurological disorders of mice and man. (Abstract) Neurosci. Abstracts 18: 395 only, 1992.
Ouardouz, M., Coderre, E., Zamponi, G. W., Hameed, S., Yin, X., Trapp, B. D., Stys, P. K. Glutamate receptors on myelinated spinal cord axons: II. AMPA and GluR5 receptors. Ann. Neurol. 65: 160-166, 2009. [PubMed: 19224531] [Full Text: https://doi.org/10.1002/ana.21539]
Paschen, W., Djuricic, B. Extent of RNA editing of glutamate receptor subunit GluR5 in different brain regions of the rat. Cell. Molec. Neurobiol. 14: 259-270, 1994. [PubMed: 7536132] [Full Text: https://doi.org/10.1007/BF02088324]
Potier, M.-C., Dutriaux, A., Lambolez, B., Bochet, P., Rossier, J. Assignment of the human glutamate receptor gene GLUR5 to 21q22 by screening a chromosome 21 YAC library. Genomics 15: 696-697, 1993. [PubMed: 8468067] [Full Text: https://doi.org/10.1006/geno.1993.1131]
Smolders, I., Bortolotto, Z. A., Clarke, V. R. J., Warre, R., Khan, G. M., O'Neill, M. J., Ornstein, P. L., Bleakman, D., Ogden, A., Weiss, B., Stables, J. P., Ho, K. H., Ebinger, G., Collingridge, G. L., Lodge, D., Michotte, Y. Antagonists of GLU-K5-containing kainate receptors prevent pilocarpine-induced limbic seizures. Nature Neurosci. 5: 796-804, 2002. [PubMed: 12080343] [Full Text: https://doi.org/10.1038/nn880]