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Gene Review

Grm6  -  glutamate receptor, metabotropic 6

Rattus norvegicus

Synonyms: Gprc1f, Metabotropic glutamate receptor 6, Mglur6, mGluR6
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High impact information on Grm6

  • Immunocytochemical and immunoelectron microscopic studies indicate that restricted localization of a specific mGluR subtype, mGluR6, at the postsynaptic site of the rat rod bipolar cell [1].
  • This specialization is developmentally regulated: mGluR6 is initially distributed in both the soma and dendrites and is finally concentrated on the postsynaptic site [1].
  • The mGluR6 localization is reversed when photoreceptors degenerate in the mutant rat with retinal dystrophy [1].
  • Evidence is thus presented indicating specialized, developmentally regulated receptor distribution in the central nervous system and the crucial role of mGluR6 in photoreceptor-bipolar cell synaptic transmission [1].
  • Molecular characterization of a novel retinal metabotropic glutamate receptor mGluR6 with a high agonist selectivity for L-2-amino-4-phosphonobutyrate [2].

Biological context of Grm6

  • A cDNA clone for a new metabotropic glutamate receptor, termed mGluR6, was isolated from a rat retinal cDNA library by cross-hybridization with the previously isolated cDNA clone for a metabotropic glutamate receptor [2].
  • Elevated IOP in DBA/2J mice significantly increased retinal gene expression of mGluR1a, mGluR2, mGluR4a, mGluR4b, mGluR6 and mGluR7a when compared to C57BL/6 control animals, while mGluR5a/b and mGluR8a were decreased and no difference was observed for mGluR3 and mGluR8b [3].
  • Recording of membrane potential showed that, similarly to the effects of retinal mGluR6 activation, L-glutamate induced membrane hyperpolarisation (-16 +/- 2 mV), which was also sensitive to group III mGluR inhibition [4].

Anatomical context of Grm6


Associations of Grm6 with chemical compounds

  • The only previous description of such an effect of L-glutamate is via activation of the group III receptor, mGluR6, in the retina [4].

Regulatory relationships of Grm6


Other interactions of Grm6

  • Quantification of the transcript levels demonstrated that mGluR6 and GluR2 genes are expressed at similar levels in rod ON-type bipolar cells [7].
  • Quantitative PCR was employed to assess gene expression levels of reference genes, PKCalpha, mGluR6 and the GluR subunits [7].
  • RESULTS: Adult RGCs predominantly expressed one or two different mGluR mRNAs, whereas juvenile RGCs coexpressed two and more. mGluR3, -5, and -7 mRNAs were found more frequently in juvenile than in adult RGCs. mGluR6 was detected in juvenile RGCs in low abundance but never in adult RGCs [6].
  • Expression patterns of mRNAs of L-AP4-sensitive metabotropic glutamate receptors (mGluR4, mGluR6, mGluR7) in the rat retina were examined by northern blot analysis and in situ hybridization histochemistry [8].
  • Expression levels of the ganglion-cell-specific transcripts Thy-1 and neurofilament and of the AII-amacrine-specific transcript parvalbumin decreased after ischemia-reperfusion, whereas the ON bipolar cell transcripts mGluR6 and PKCalpha did not show ischemia-induced changes [9].

Analytical, diagnostic and therapeutic context of Grm6

  • Blot and in situ hybridization analyses indicated that mGluR6 mRNA is restrictedly expressed in the inner nuclear layer of the retina where ON-bipolar cells are distributed [2].
  • Single cells with a bipolar morphology were harvested, subjected to multiplex PCR with protein kinase C (PKC)-, mGluR6- and GluR1-4-specific primers, followed by a real-time quantitative PCR assay [7].


  1. Developmentally regulated postsynaptic localization of a metabotropic glutamate receptor in rat rod bipolar cells. Nomura, A., Shigemoto, R., Nakamura, Y., Okamoto, N., Mizuno, N., Nakanishi, S. Cell (1994) [Pubmed]
  2. Molecular characterization of a novel retinal metabotropic glutamate receptor mGluR6 with a high agonist selectivity for L-2-amino-4-phosphonobutyrate. Nakajima, Y., Iwakabe, H., Akazawa, C., Nawa, H., Shigemoto, R., Mizuno, N., Nakanishi, S. J. Biol. Chem. (1993) [Pubmed]
  3. Metabotropic glutamate receptors are differentially regulated under elevated intraocular pressure. Dyka, F.M., May, C.A., Enz, R. J. Neurochem. (2004) [Pubmed]
  4. Group III metabotropic glutamate receptor activation inhibits Ca2+ influx and nitric oxide synthase activity in bone marrow stromal cells. Foreman, M.A., Gu, Y., Howl, J.D., Jones, S., Publicover, S.J. J. Cell. Physiol. (2005) [Pubmed]
  5. mGluR3 and mGluR5 are the predominant metabotropic glutamate receptor mRNAs expressed in hippocampal astrocytes acutely isolated from young rats. Schools, G.P., Kimelberg, H.K. J. Neurosci. Res. (1999) [Pubmed]
  6. Coexpression patterns of mGLuR mRNAs in rat retinal ganglion cells: a single-cell RT-PCR study. Tehrani, A., Wheeler-Schilling, T.H., Guenther, E. Invest. Ophthalmol. Vis. Sci. (2000) [Pubmed]
  7. Gene expression of AMPA-type glutamate receptor subunits in rod-type ON bipolar cells of rat retina. Kamphuis, W., Dijk, F., O'Brien, B.J. Eur. J. Neurosci. (2003) [Pubmed]
  8. Expression of mRNAs of L-AP4-sensitive metabotropic glutamate receptors (mGluR4, mGluR6, mGluR7) in the rat retina. Akazawa, C., Ohishi, H., Nakajima, Y., Okamoto, N., Shigemoto, R., Nakanishi, S., Mizuno, N. Neurosci. Lett. (1994) [Pubmed]
  9. Ischemia-induced changes of AMPA-type glutamate receptor subunit expression pattern in the rat retina: a real-time quantitative PCR study. Dijk, F., Kraal-Muller, E., Kamphuis, W. Invest. Ophthalmol. Vis. Sci. (2004) [Pubmed]
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