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

• Using Western blotting and RT-PCR we detected mGluR6 protein and transcripts in marrow stromal cells [4].
• In this study, therefore, we examined expression of mRNA for all the mGluRs except mGluR6 by single-cell reverse transcriptase-polymerase chain reaction (RT-PCR) in freshly isolated hippocampal astrocytes from postnatal day P1-10 rats, as an additional approach to address the question of which mGluRs are expressed on astrocytes in situ [5].
• The mGluR5 PCR products were primarily of the "a" splice variant. mGluR1, 2, 4, 7, and 8 were very rarely or never detected. mGluR6 mRNA level was too low in whole rat brain and hippocampus to warrant examination [5].

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

• However, mGluR6 was expressed in adult RGCs after axotomy. mGluR1 and -7 were also found more frequently in axotomized RGCs than in the adult control group [6].

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].

References