Gene Symbol: Grm6
Description: glutamate receptor, metabotropic 6
Alias: BC021919, Gm3, Gprc1f, mGluR6, nerg1, nob2, nob3, nob4, metabotropic glutamate receptor 6, G protein-coupled receptor GRM6, G protein-coupled receptor, family C, group 1, member F
Species: mouse
Products:     Grm6

Top Publications

  1. Iwakabe H, Katsuura G, Ishibashi C, Nakanishi S. Impairment of pupillary responses and optokinetic nystagmus in the mGluR6-deficient mouse. Neuropharmacology. 1997;36:135-43 pubmed
    ..The segregation of ON responses involves a G protein-coupled metabotropic glutamate receptor (mGluR). The mGluR6 subtype is expressed restrictedly at the postsynaptic site of retinal ON-bipolar cells...
  2. Sugihara H, Inoue T, Nakanishi S, Fukuda Y. A late ON response remains in visual response of the mGluR6-deficient mouse. Neurosci Lett. 1997;233:137-40 pubmed
    ..ON response recorded from the superior colliculus is absent in the metabotropic glutamate receptor subtype 6 (mGluR6) knockout mice...
  3. Tagawa Y, Sawai H, Ueda Y, Tauchi M, Nakanishi S. Immunohistological studies of metabotropic glutamate receptor subtype 6-deficient mice show no abnormality of retinal cell organization and ganglion cell maturation. J Neurosci. 1999;19:2568-79 pubmed
    ..Gene-targeted ablation of mGluR6 specifically expressed in ON bipolar cells blocks normal ON responses but has been predicted to enhance glutamate ..
  4. Quraishi S, Gayet J, Morgans C, Duvoisin R. Distribution of group-III metabotropic glutamate receptors in the retina. J Comp Neurol. 2007;501:931-43 pubmed
    ..b>mGluR6 expression was limited to the outer plexiform layer...
  5. Cao Y, Masuho I, Okawa H, Xie K, Asami J, Kammermeier P, et al. Retina-specific GTPase accelerator RGS11/G beta 5S/R9AP is a constitutive heterotrimer selectively targeted to mGluR6 in ON-bipolar neurons. J Neurosci. 2009;29:9301-13 pubmed publisher
    ..the dendritic tips of ON-bipolar cells in which its localization is accomplished through a direct association with mGluR6, the glutamate receptor essential for the ON-bipolar light response...
  6. Tsukamoto Y, Omi N. Effects of mGluR6-deficiency on photoreceptor ribbon synapse formation: comparison of electron microscopic analysis of serial sections with random sections. Vis Neurosci. 2014;31:39-46 pubmed publisher
    This study examined the effects of metabotropic glutamate receptor 6 (mGluR6) deficiency on ribbon synapse formation in rod spherules and cone pedicles using serial-section electron microscopy...
  7. Maddox D, Vessey K, Yarbrough G, Invergo B, Cantrell D, Inayat S, et al. Allelic variance between GRM6 mutants, Grm6nob3 and Grm6nob4 results in differences in retinal ganglion cell visual responses. J Physiol. 2008;586:4409-24 pubmed publisher
    ..The nob3 phenotype mapped to chromosome 11 in a region containing the metabotropic glutamate receptor 6 gene (Grm6)...
  8. Friedman J, Chang B, Krauth D, Lopez I, Waseem N, Hurd R, et al. Loss of lysophosphatidylcholine acyltransferase 1 leads to photoreceptor degeneration in rd11 mice. Proc Natl Acad Sci U S A. 2010;107:15523-8 pubmed publisher
    ..Our studies add another dimension to an essential role for LPCAT1 in retinal photoreceptor homeostasis. ..
  9. Klooster J, van Genderen M, Yu M, Florijn R, Riemslag F, Bergen A, et al. Ultrastructural localization of GPR179 and the impact of mutant forms on retinal function in CSNB1 patients and a mouse model. Invest Ophthalmol Vis Sci. 2013;54:6973-81 pubmed publisher
    ..15-Hz flicker ERG abnormalities of Gpr179(nob5) and Grm6(nob3) mice were comparable...

More Information


  1. Thompson S, Stasheff S, Hernandez J, Nylen E, East J, Kardon R, et al. Different inner retinal pathways mediate rod-cone input in irradiance detection for the pupillary light reflex and regulation of behavioral state in mice. Invest Ophthalmol Vis Sci. 2011;52:618-23 pubmed publisher
    ..masking (activity suppression by light) was measured in wild-type mice with intact inner retinal circuitry, Nob4 mice that lack ON-bipolar cell function, and rd1 mice that lack rods and cones and, therefore, have no input to ON ..
  2. Tang Z, El Far O, Betz H, Scheschonka A. Pias1 interaction and sumoylation of metabotropic glutamate receptor 8. J Biol Chem. 2005;280:38153-9 pubmed
    ..Our results are consistent with post-translational sumoylation providing a novel mechanism of group III mGluR regulation. ..
  3. Armata I, Giompres P, Smith A, Stasi K, Kouvelas E, Mitsacos A. Genetically induced retinal degeneration leads to changes in metabotropic glutamate receptor expression. Neurosci Lett. 2006;393:12-7 pubmed ON-cone and rod bipolar cells is sign reversing and mediated by the metabotropic glutamate receptor mGluR6, which converts the light-evoked hyperpolarization of the photoreceptors into depolarization of ON bipolar cells...
  4. Takao M, Morigiwa K, Sasaki H, Miyoshi T, Shima T, Nakanishi S, et al. Impaired behavioral suppression by light in metabotropic glutamate receptor subtype 6-deficient mice. Neuroscience. 2000;97:779-87 pubmed
    ..This study clearly demonstrates that the dysfunction of the ON visual pathway in metabotropic glutamate receptor subtype 6-deficient mice impairs their behavioral responsiveness to light and yet preserves their circadian system. ..
  5. Peachey N, Pearring J, Bojang P, Hirschtritt M, Sturgill Short G, Ray T, et al. Depolarizing bipolar cell dysfunction due to a Trpm1 point mutation. J Neurophysiol. 2012;108:2442-51 pubmed publisher
    ..The Trpm1(tvrm27/tvrm27) mutant will be useful for elucidating the role of TRPM1 in DBC signal transduction, for determining how Trpm1 mutations impact central visual processing, and for evaluating experimental therapies for cCSNB...
  6. Pinto L, Vitaterna M, Shimomura K, Siepka S, Balannik V, McDearmon E, et al. Generation, identification and functional characterization of the nob4 mutation of Grm6 in the mouse. Vis Neurosci. 2007;24:111-23 pubmed chromosome 11 in a region containing the Grm6 gene, which encodes a metabotropic glutamate receptor protein, mGluR6. Sequencing confirmed a single nucleotide substitution from T to C in the Grm6 gene...
  7. Xu Y, Dhingra A, Fina M, Koike C, Furukawa T, Vardi N. mGluR6 deletion renders the TRPM1 channel in retina inactive. J Neurophysiol. 2012;107:948-57 pubmed publisher
    In darkness, glutamate released from photoreceptors activates the metabotropic glutamate receptor 6 (mGluR6) on retinal ON bipolar cells...
  8. Gschwind M, Huber G. Introduction of hereditary disease-associated mutations into the beta-amyloid precursor protein gene of mouse embryonic stem cells: a comparison of homologous recombination methods. Mol Cell Biol. 1998;18:4651-8 pubmed
    ..For further improvements, optimization of the homologous recombination efficiency could be envisaged. ..
  9. Masu M, Iwakabe H, Tagawa Y, Miyoshi T, Yamashita M, Fukuda Y, et al. Specific deficit of the ON response in visual transmission by targeted disruption of the mGluR6 gene. Cell. 1995;80:757-65 pubmed
    Taking advantage of the restricted expression of metabotropic glutamate receptor subtype 6 (mGluR6) in retinal ON bipolar cells, we generated knockout mice lacking mGluR6 expression...
  10. Dhingra A, Ramakrishnan H, Neinstein A, Fina M, Xu Y, Li J, et al. G?3 is required for normal light ON responses and synaptic maintenance. J Neurosci. 2012;32:11343-55 pubmed publisher
    ..In the ON bipolar cells, mGluR6 inverts the photoreceptor's signal via a cascade in which glutamate released from photoreceptors closes the TRPM1 ..
  11. Morgans C, Wensel T, Brown R, Perez Leon J, Bearnot B, Duvoisin R. Gbeta5-RGS complexes co-localize with mGluR6 in retinal ON-bipolar cells. Eur J Neurosci. 2007;26:2899-905 pubmed
    ..rapid inactivation of the G protein Galphao, which is activated in the dark by metabotropic glutamate receptor, mGluR6, in their dendritic tips...
  12. Vogel H, Nestler M, Ruschendorf F, Block M, Tischer S, Kluge R, et al. Characterization of Nob3, a major quantitative trait locus for obesity and hyperglycemia on mouse chromosome 1. Physiol Genomics. 2009;38:226-32 pubmed publisher
    ..x B6)F2 intercross population were predominantly due to a broad quantitative trait locus (QTL) on chromosome 1 (Nob3; logarithm of the odds score 16.1, 16.0, 4...
  13. Kozuka T, Chaya T, Tamalu F, Shimada M, Fujimaki Aoba K, Kuwahara R, et al. The TRPM1 Channel Is Required for Development of the Rod ON Bipolar Cell-AII Amacrine Cell Pathway in the Retinal Circuit. J Neurosci. 2017;37:9889-9900 pubmed publisher
    ..were not caused by a disruption of total glutamate transmission due to loss of the ON bipolar glutamate receptor mGluR6 or the photoreceptor glutamate transporter VGluT1...
  14. Koyasu T, Kondo M, Miyata K, Ueno S, Miyata T, Nishizawa Y, et al. Photopic electroretinograms of mGluR6-deficient mice. Curr Eye Res. 2008;33:91-9 pubmed publisher
    To study the properties of the photopic electroretinograms (ERGs) of the metabotropic glutamate receptor subtype 6 (mGluR6)-deficient mice and to investigate the contribution of cone ON-and OFF-pathways to the mouse photopic ERGs...
  15. Koike C, Obara T, Uriu Y, Numata T, Sanuki R, Miyata K, et al. TRPM1 is a component of the retinal ON bipolar cell transduction channel in the mGluR6 cascade. Proc Natl Acad Sci U S A. 2010;107:332-7 pubmed publisher
    ..Glutamate released from photoreceptors modulates the photoresponse of ON BCs via metabotropic glutamate receptor 6 (mGluR6) and G protein (Go) that regulates a cation channel...
  16. Kaupmann K, Huggel K, Heid J, Flor P, Bischoff S, Mickel S, et al. Expression cloning of GABA(B) receptors uncovers similarity to metabotropic glutamate receptors. Nature. 1997;386:239-46 pubmed
    ..The cloned receptors negatively couple to adenylyl cyclase and show sequence similarity to the metabotropic receptors for the excitatory neurotransmitter L-glutamate. ..
  17. Qian H, Ji R, Gregg R, Peachey N. Identification of a new mutant allele, Grm6(nob7), for complete congenital stationary night blindness. Vis Neurosci. 2015;32:E004 pubmed publisher
    ..8 and 9, which would result in a frameshift mutation in the open reading frame that encodes the metabotropic glutamate receptor 6 (Grm6)...
  18. Chakraborty R, Park H, Hanif A, Sidhu C, Iuvone P, Pardue M. ON pathway mutations increase susceptibility to form-deprivation myopia. Exp Eye Res. 2015;137:79-83 pubmed publisher
    ..In this study, we used mGluR6-/- mice, another ON pathway mutant, to determine whether the nob phenotype was due to the Nyx mutation or abnormal ..
  19. Masugi M, Yokoi M, Shigemoto R, Muguruma K, Watanabe Y, Sansig G, et al. Metabotropic glutamate receptor subtype 7 ablation causes deficit in fear response and conditioned taste aversion. J Neurosci. 1999;19:955-63 pubmed
    ..Together, these findings strongly suggest that mGluR7 is involved in neural processes subserving amygdala-dependent averse responses. ..
  20. Vardi T, Fina M, Zhang L, Dhingra A, Vardi N. mGluR6 transcripts in non-neuronal tissues. J Histochem Cytochem. 2011;59:1076-86 pubmed publisher
    To study mGluR6 expression, the authors investigated two transgenic mouse lines that express enhanced green fluorescent protein (GFP) under control of mGluR6 promoter...
  21. Martins R, Zindy F, Donovan S, Zhang J, Pounds S, Wey A, et al. N-myc coordinates retinal growth with eye size during mouse development. Genes Dev. 2008;22:179-93 pubmed publisher
    ..We propose that N-myc lies upstream of the cell cycle machinery in the developing mouse retina and thus coordinates the growth of both the retina and eye through extrinsic cues. ..
  22. Xue Y, Shen S, Corbo J, Kefalov V. Circadian and light-driven regulation of rod dark adaptation. Sci Rep. 2015;5:17616 pubmed publisher
    ..This daily melatonin-driven modulation of rod dark adaptation could potentially protect the retina from light-induced damage during the day. ..
  23. Kominami T, Ueno S, Nakanishi A, Kominami A, Kondo M, Furukawa T, et al. Temporal Properties of Cone ERGs of Pikachurin Null Mutant Mouse. Invest Ophthalmol Vis Sci. 2016;57:1264-9 pubmed publisher
    ..Flicker ERGs were recorded from wild-type (WT), Pika-/-, and mGluR6 null mutant (mGluR6-/-) mice. The frequency of stimulation was 3.906 to 31.250 Hz...
  24. Cao Y, Sarria I, Fehlhaber K, Kamasawa N, Orlandi C, James K, et al. Mechanism for Selective Synaptic Wiring of Rod Photoreceptors into the Retinal Circuitry and Its Role in Vision. Neuron. 2015;87:1248-60 pubmed publisher
    ..At the synapse, ELFN1 binds in trans to mGluR6, the postsynaptic receptor on rod ON-bipolar cells...
  25. Huynh N, Jeffrey B, Turriff A, Sieving P, Cukras C. Sorting out co-occurrence of rare monogenic retinopathies: Stargardt disease co-existing with congenital stationary night blindness. Ophthalmic Genet. 2014;35:51-6 pubmed publisher
    ..Here, we report a case of Stargardt disease and congenital stationary night blindness (CSNB) in the same patient, and the identification of two novel in-frame deletions in the GRM6 gene.
  26. Ray T, Heath K, Hasan N, Noel J, SAMUELS I, Martemyanov K, et al. GPR179 is required for high sensitivity of the mGluR6 signaling cascade in depolarizing bipolar cells. J Neurosci. 2014;34:6334-43 pubmed publisher
    ..For normal function, ON or depolarizing bipolar cells (DBCs) require the G-protein-coupled receptor, mGluR6, an intact G-protein-coupled cascade and the transient receptor potential melastatin 1 (TRPM1) cation channel...
  27. Cao Y, Posokhova E, Martemyanov K. TRPM1 forms complexes with nyctalopin in vivo and accumulates in postsynaptic compartment of ON-bipolar neurons in mGluR6-dependent manner. J Neurosci. 2011;31:11521-6 pubmed publisher
    ..This process is mediated by the G-protein-coupled receptor pathway involving glutamate receptor mGluR6 and effector channel TRPM1...
  28. Clements R, Turk R, Campbell K, Wright K. Dystroglycan Maintains Inner Limiting Membrane Integrity to Coordinate Retinal Development. J Neurosci. 2017;37:8559-8574 pubmed publisher
    ..These results demonstrate that disorganization of retinal circuit development is a likely contributor to visual dysfunction in patients with dystroglycanopathy. ..
  29. Wang Y, Fehlhaber K, Sarria I, Cao Y, Ingram N, Guerrero Given D, et al. The Auxiliary Calcium Channel Subunit α2δ4 Is Required for Axonal Elaboration, Synaptic Transmission, and Wiring of Rod Photoreceptors. Neuron. 2017;93:1359-1374.e6 pubmed publisher
    ..4) with postsynaptic mGluR6 receptors...
  30. Tummala S, Neinstein A, Fina M, Dhingra A, Vardi N. Localization of Cacna1s to ON bipolar dendritic tips requires mGluR6-related cascade elements. Invest Ophthalmol Vis Sci. 2014;55:1483-92 pubmed publisher
    ..channels is also expressed postsynaptically at the tips of ON bipolar cell dendrites where it colocalizes with mGluR6, but has an unknown function...
  31. RENTERIA R, Tian N, Cang J, Nakanishi S, Stryker M, Copenhagen D. Intrinsic ON responses of the retinal OFF pathway are suppressed by the ON pathway. J Neurosci. 2006;26:11857-69 pubmed
    ..ON responses are thought to originate by exclusive use of metabotropic glutamate receptor 6 (mGluR6) expressed in retinal ON bipolar cells...
  32. Sugita Y, Miura K, Araki F, Furukawa T, Kawano K. Contributions of retinal direction-selective ganglion cells to optokinetic responses in mice. Eur J Neurosci. 2013;38:2823-31 pubmed publisher
  33. Ueda Y, Iwakabe H, Masu M, Suzuki M, Nakanishi S. The mGluR6 5' upstream transgene sequence directs a cell-specific and developmentally regulated expression in retinal rod and ON-type cone bipolar cells. J Neurosci. 1997;17:3014-23 pubmed
    ..5 kilobase pairs of the 5' upstream sequence from the mouse metabotropic glutamate receptor subtype 6 (mGluR6) gene fused to the beta-galactosidase (lacZ) reporter gene, and investigated the promoter function of the cell-..
  34. Tummala S, Dhingra A, Fina M, Li J, Ramakrishnan H, Vardi N. Lack of mGluR6-related cascade elements leads to retrograde trans-synaptic effects on rod photoreceptor synapses via matrix-associated proteins. Eur J Neurosci. 2016;43:1509-22 pubmed publisher
    ..In retinal ON bipolar cells, Go couples the metabotropic receptor mGluR6 to the TRPM1 channel and closes it in the dark, thus hyperpolarizing the cell...
  35. Peachey N, Hasan N, FitzMaurice B, Burrill S, Pangeni G, Karst S, et al. A missense mutation in Grm6 reduces but does not eliminate mGluR6 expression or rod depolarizing bipolar cell function. J Neurophysiol. 2017;118:845-854 pubmed publisher
    i>GRM6 encodes the metabotropic glutamate receptor 6 (mGluR6) used by retinal depolarizing bipolar cells (DBCs)...