L-glutamate is the major excitatoryneurotransmitter in thecentral nervous system and activates both ionotropic and metabotropic glutamate receptors. Glutamatergic neurotransmission is involved in most aspects of normal brain function and can be perturbed in many neuropathologic conditions. Themetabotropic glutamate receptors are a family ofG protein-coupled receptors, that have been divided into 3 groups on the basis of sequence homology, putative signal transduction mechanisms, and pharmacologic properties. Group I includesGRM1 andGRM5 and these receptors have been shown to activatephospholipase C. Group II includesGRM2 andGRM3, while Group III includesGRM4, GRM6,GRM7 andGRM8. Group II and III receptors are linked to the inhibition of thecyclic AMP cascade but differ in their agonist selectivities.[5]
mGluR6 is specifically expressed in the retina, in a subtype of bipolar cells thatdepolarize in response to light, known as ON bipolar cells. These cells formsynapses with photoreceptor cells, and detect theneurotransmitter glutamate via a GPCR signal transduction cascade. The glutamate receptor mGluR6 is located post-synaptically at the tips of the bipolar celldendrites, and is responsible for initiating a signaling cascade that ultimately controls gating of theTRPM1 channel.[7][8] In human patients, mutations in theGRM6 gene are associated withcongenital stationary night blindness.[9][10]
^Hashimoto T, Inazawa J, Okamoto N, Tagawa Y, Bessho Y, Honda Y, Nakanishi S (June 1997). "The whole nucleotide sequence and chromosomal localization of the gene for human metabotropic glutamate receptor subtype 6".Eur. J. Neurosci.9 (6):1226–35.doi:10.1111/j.1460-9568.1997.tb01477.x.PMID9215706.S2CID25387864.
^Zeitz C, van Genderen M, Neidhardt J, Luhmann UF, Hoeben F, Forster U, Wycisk K, Mátyás G, Hoyng CB, Riemslag F, Meire F, Cremers FP, Berger W (2005). "Mutations in GRM6 cause autosomal recessive congenital stationary night blindness with a distinctive scotopic 15-Hz flicker electroretinogram".Invest Ophthalmol Vis Sci.46 (11):4328–35.doi:10.1167/iovs.05-0526.PMID16249515.
Hashimoto T, Inazawa J, Okamoto N, et al. (1997). "The whole nucleotide sequence and chromosomal localization of the gene for human metabotropic glutamate receptor subtype 6".Eur. J. Neurosci.9 (6):1226–35.doi:10.1111/j.1460-9568.1997.tb01477.x.PMID9215706.S2CID25387864.
Valerio A, Ferraboli S, Paterlini M, et al. (2001). "Identification of novel alternatively-spliced mRNA isoforms of metabotropic glutamate receptor 6 gene in rat and human retina".Gene.262 (1–2):99–106.doi:10.1016/S0378-1119(00)00547-3.PMID11179672.
Zeitz C, van Genderen M, Neidhardt J, et al. (2005). "Mutations in GRM6 cause autosomal recessive congenital stationary night blindness with a distinctive scotopic 15-Hz flicker electroretinogram".Invest. Ophthalmol. Vis. Sci.46 (11):4328–35.doi:10.1167/iovs.05-0526.PMID16249515.
Zeitz C, Forster U, Neidhardt J, et al. (2007). "Night blindness-associated mutations in the ligand-binding, cysteine-rich, and intracellular domains of the metabotropic glutamate receptor 6 abolish protein trafficking".Hum. Mutat.28 (8):771–80.doi:10.1002/humu.20499.PMID17405131.S2CID24946081.
