L-glutamate is the major excitatory neurotransmitter in the central 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. The metabotropic glutamate receptors are a family of G 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 includes GRM1 and GRM5 and these receptors have been shown to activate phospholipase C. Group II includes GRM2 and GRM3, while Group III includes GRM4, GRM6, GRM7 and GRM8. Group II and III receptors are linked to the inhibition of the cyclic AMP cascade but differ in their agonist selectivities.[1]
mGluR6 is specifically expressed in the retina, in a subtype of bipolar cells that depolarize in response to light. These cells form synapses with photoreceptor cells, and detect the neurotransmitter glutamate via a GPCR signal transduction cascade. The glutamate receptor mGluR6 is located post-synaptically at the tips of the bipolar cell dendrites, and is responsible for initiating the signaling cascade.[3][4] In human patients, mutations in the GRM6 gene are associated with congenital stationary night blindness.[5][6]
↑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.
↑Nakajima Y, Iwakabe H, Akazawa C, Nawa H, Shigemoto R, Mizuno N, Nakanishi S (1993). "Molecular characterization of a novel retinal metabotropic glutamate receptor mGluR6 with a high agonist selectivity for L-2-amino-4-phosphonobutyrate". J Biol Chem. 268 (16): 11868–73. PMID8389366.
↑Masu M, Iwakabe H, Tagawa Y, Miyoshi T, Yamashita M, Fukuda Y, Sasaki H, Hiroi K, Nakamura Y, Shigemoto R, Takada M, Nakamura K, Nakao K, Katsuki M, Nakanishi S (1995). "Specific deficit of the ON response in visual transmission by targeted disruption of the mGluR6 gene". Cell. 80 (5): 757–65. PMID7889569.
↑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.
Dhingra A, Lyubarsky A, Jiang M, et al. (2001). "The light response of ON bipolar neurons requires G[alpha]o". J. Neurosci. 20 (24): 9053–8. PMID11124982.
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.
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