Affinage

GRM6

Metabotropic glutamate receptor 6 · UniProt O15303

Length
877 aa
Mass
95.5 kDa
Annotated
2026-04-28
71 papers in source corpus 27 papers cited in narrative 27 extracted findings

Mechanistic narrative

Synthesis pass · prose summary of the discoveries below

GRM6 (mGluR6) is the metabotropic glutamate receptor that initiates the ON visual pathway by transducing photoreceptor glutamate release into a sign-inverting signal in retinal ON bipolar cells. Upon glutamate binding, mGluR6 activates Gαo, which closes the constitutively active TRPM1 cation channel, hyperpolarizing the cell in darkness; light-evoked reduction in glutamate deactivates mGluR6, permitting TRPM1 to open and depolarize ON bipolar cells (PMID:7889569, PMID:10191311, PMID:19966281). The receptor operates within a dendritic-tip macromolecular complex comprising nyctalopin, TRPM1, GPR179, and RGS7/RGS11–Gβ5–R9AP GTPase-accelerating modules, whose postsynaptic localization depends on mGluR6 and whose GAP activity sets the kinetics of Gαo deactivation (PMID:21832182, PMID:24790204, PMID:20007977). Synaptic targeting of mGluR6 itself requires trans-synaptic binding to presynaptic ELFN1/ELFN2 through its complex N-glycosylated ligand-binding domain, while C-terminal ER-retention motifs regulate ER-to-Golgi trafficking and homodimeric quality control; loss-of-function mutations in these domains cause congenital stationary night blindness (CSNB) (PMID:38428819, PMID:39681475, PMID:33067823, PMID:19666700).

Mechanistic history

Synthesis pass · year-by-year structured walk · 18 steps
  1. 1993 High

    Identification of mGluR6 as a retina-specific Group III metabotropic glutamate receptor that inhibits cAMP via G-protein coupling established the molecular identity of the long-sought ON bipolar cell glutamate receptor.

    Evidence cDNA cloning, heterologous expression in CHO cells with cAMP assay, in situ hybridization showing inner nuclear layer expression

    PMID:8389366

    Open questions at the time
    • Downstream effector channel unknown
    • Identity of the coupled G protein in ON bipolar cells unresolved
    • No in vivo loss-of-function evidence
  2. 1995 High

    Genetic ablation demonstrated that mGluR6 is the essential and non-redundant receptor for ON-pathway signaling, resolving whether other glutamate receptors could substitute.

    Evidence mGluR6 knockout mice lacked ON responses (ERG b-wave) while retaining OFF responses; retinal organization was normal

    PMID:7889569

    Open questions at the time
    • Identity of downstream channel unknown
    • Mechanism of signal transduction from receptor to channel not established
  3. 1999 High

    Electrophysiological dialysis experiments identified Gαo as the obligatory transducer coupling mGluR6 to the cation channel, ruling out cGMP-PDE cascades and establishing a G-protein-gated channel mechanism.

    Evidence Whole-cell patch clamp with Gαo protein dialysis and anti-Gαo antibody in ON bipolar cells

    PMID:10191311

    Open questions at the time
    • Molecular identity of the cation channel unknown
    • How Gαo closes the channel not determined
  4. 2000 High

    Ultrastructural localization of mGluR6 at the base of postsynaptic triads in rod and cone ON bipolar dendrites defined the nanoscale signaling geometry, and Ca²⁺-dependent run-down of the glutamate response revealed an intrinsic adaptation mechanism.

    Evidence Immunoelectron microscopy across three species; patch-clamp with Ca²⁺ chelators in salamander slices

    PMID:10844016 PMID:10870081

    Open questions at the time
    • Molecular basis of Ca²⁺-dependent desensitization unknown
    • Channel identity still unresolved
  5. 2002 High

    Identification of calcineurin as the Ca²⁺-dependent phosphatase mediating desensitization of the mGluR6 transduction current provided the first molecular mechanism for adaptation in ON bipolar cells.

    Evidence Patch-clamp with calcineurin inhibitors and constitutively active CaN420 dialysis

    PMID:12205131

    Open questions at the time
    • Calcineurin substrate in the cascade not identified
    • Whether calcineurin acts on channel or upstream components unclear
  6. 2006 High

    Systematic G-protein coupling analysis established Gαo as the preferred subunit (Gαoa > Gαob ≫ others) and confirmed by single-cell RT-PCR that Gαo is the sole relevant Gα in ON bipolar cells, resolving coupling specificity.

    Evidence Reconstitution in sympathetic neurons with PTX-insensitive Gα mutants; single-cell RT-PCR

    PMID:17266783

    Open questions at the time
    • Structural basis of Gαo selectivity unknown
    • Which Gβγ pairs participate in vivo not resolved
  7. 2007 High

    Discovery that RGS7–Gβ5 and RGS11–Gβ5 complexes co-localize with mGluR6 and depend on it for postsynaptic positioning revealed that mGluR6 organizes its own deactivation machinery.

    Evidence Co-immunoprecipitation and immunofluorescence in mGluR6 knockout mice

    PMID:18001285

    Open questions at the time
    • Direct binding interface between mGluR6 and RGS complexes not mapped
    • Functional consequence of RGS mislocalization on kinetics not measured
  8. 2009 High

    Three concurrent advances — identification of TRPM1 as the effector channel, reconstitution of R9AP-mediated potentiation of RGS11–Gβ5 GAP activity on Gαo, and demonstration that R9AP and mGluR6 jointly stabilize the RGS11 complex — completed the core signaling cascade from receptor to channel with its kinetic regulators.

    Evidence TRPM1 null mice (ERG + patch clamp), Xenopus oocyte reconstitution of GAP activity, co-IP and KO immunolocalization

    PMID:19625520 PMID:19966281 PMID:20007977

    Open questions at the time
    • How Gαo-GTP closes TRPM1 is mechanistically unclear
    • Whether Gβγ also regulates TRPM1 not resolved
  9. 2009 Medium

    A CSNB-associated mGluR6 point mutation (E775K) that selectively ablates Gαo coupling while retaining Gi coupling provided the first mechanistic link between disease mutations and altered G-protein selectivity.

    Evidence Heterologous G-protein coupling and trafficking assays in sympathetic neurons

    PMID:19666700

    Open questions at the time
    • Structural basis of Gαo vs Gi selectivity at this residue not determined
    • Patient phenotype-genotype correlation limited to single mutation
  10. 2011 High

    Identification of nyctalopin as a scaffold interacting with both TRPM1 and mGluR6, together with evidence that mGluR6 is required for TRPM1 dendritic tip targeting and constitutive activity, established mGluR6 as the organizer of a macromolecular signaling complex.

    Evidence Mass spectrometry screen, co-IP, mGluR6-null patch clamp and immunostaining

    PMID:21832182 PMID:22131384

    Open questions at the time
    • Direct vs indirect interaction between mGluR6 and nyctalopin not resolved
    • Mechanism by which mGluR6 enables TRPM1 constitutive activity unknown
  11. 2014 High

    GPR179 was identified as an additional scaffold that recruits RGS7/RGS11 to dendritic tips and directly modulates TRPM1 gating, adding a second orphan receptor to the mGluR6 signalosome and revealing multi-level regulation of cascade sensitivity.

    Evidence Gpr179(nob5) mouse ERG, noise analysis, pharmacological gating comparison with RGS7/11 double KO

    PMID:24790204

    Open questions at the time
    • How GPR179 directly gates TRPM1 not structurally resolved
    • Whether GPR179 and mGluR6 form a direct heteromeric complex unknown
  12. 2020 Medium

    Identification of basic-residue ER retention motifs in the mGluR6 C-terminal domain revealed a quality-control mechanism governing ER-to-Golgi trafficking and explained how CTD truncations impair surface expression.

    Evidence Surface biotinylation, site-directed mutagenesis, electrophysiology in 293T cells and hippocampal neurons

    PMID:33067823

    Open questions at the time
    • ER retention binding partner not identified
    • Whether this mechanism operates in ON bipolar cells in vivo not shown
  13. 2021 High

    Dissection of domain requirements showed that the ligand-binding domain mediates ELFN1 binding and synaptic targeting while the C-terminus is dispensable for targeting but required for TRPM1 trafficking, separating localization from effector assembly functions.

    Evidence AAV-driven LBD deletion mutants in mGluR6-null mice, ELFN1 pulldown, immunohistochemistry

    PMID:34793838

    Open questions at the time
    • Binding interface residues between LBD and ELFN1 not mapped
    • How CTD contributes to TRPM1 trafficking mechanistically unclear
  14. 2023 Medium

    Demonstration that ER-retained mGluR6 mutants dominantly suppress surface expression of wild-type mGluR6 via homodimerization provided a molecular mechanism for dominant-negative pathogenicity in heterozygous CSNB patients.

    Evidence Flow cytometry, co-immunoprecipitation, site-directed mutagenesis in 293T cells

    PMID:37352898

    Open questions at the time
    • In vivo relevance in heterozygous animal model not tested
    • Stoichiometry of heterodimeric trapping not quantified
  15. 2024 High

    Complex N-glycosylation (particularly at N445) was shown to be essential for trans-synaptic ELFN1/ELFN2 binding and dendritic tip localization, while CSNB missense mutations in the LBD cause Golgi bypass and loss of ELFN1 binding despite reaching the plasma membrane, unifying glycosylation quality control with disease mechanism.

    Evidence Glycosidase treatment, N-glycosylation site mutagenesis, ELFN pulldown, immunohistochemistry in bipolar cells

    PMID:38428819 PMID:39681475

    Open questions at the time
    • Whether Golgi bypass is due to misfolding or a specific sorting signal is unresolved
    • Structural basis of glycan-dependent ELFN recognition unknown
  16. 2025 High

    Bidirectional trans-synaptic stabilization between mGluR6 and ELFN1 was established, and the ELFN1 LRR/LRRCT domains were shown to be necessary and sufficient for mGluR6 binding, completing the molecular anatomy of the photoreceptor–ON bipolar synapse organizer.

    Evidence In vitro binding with ELFN1 domain deletion mutants, mGluR6-null AAV rescue, immunofluorescence

    PMID:40930976

    Open questions at the time
    • Atomic-resolution structure of the mGluR6–ELFN1 complex not available
    • Contribution of ELFN2 vs ELFN1 to cone vs rod synapses not fully delineated
  17. 2025 Medium

    Systematic LBD deletions revealed that the upper lobe regulates ER-to-Golgi sorting — small deletions cause unconventional secretion while larger deletions partially restore conventional trafficking — establishing a structural checkpoint in the secretory pathway.

    Evidence Glycosidase assays, surface biotinylation, heterologous expression of deletion mutants

    PMID:41448371

    Open questions at the time
    • Sorting receptor recognizing the upper lobe not identified
    • In vivo relevance for bipolar cell surface delivery not tested
  18. 2026 High

    A cryo-EM structure of agonist-bound mGluR6 revealed that glutamate induces asymmetric homodimerization and pre-organizes the transmembrane domain interface for Gαo coupling through a noncanonical CRD–ECL2 contact, providing the first structural framework for activation.

    Evidence Cryo-EM structure determination, mutagenesis of CRD–ECL2 interface with Gαo coupling and surface trafficking assays

    PMID:41803130

    Open questions at the time
    • Structure of the mGluR6–Gαo complex not yet resolved
    • How asymmetry translates to selective Gαo over Gi coupling remains unclear

Open questions

Synthesis pass · forward-looking unresolved questions
  • The direct mechanism by which Gαo-GTP closes the TRPM1 channel — whether by direct binding, via an intermediary, or through membrane-delimited signaling — remains the central unresolved question in the mGluR6 cascade.
  • Gαo–TRPM1 direct interaction not demonstrated biochemically or structurally
  • Role of Gβγ subunits in TRPM1 modulation unresolved
  • Calcineurin substrate in the desensitization pathway not identified

Mechanism profile

Synthesis pass · controlled-vocabulary classification · explore literature graph →
Molecular activity
GO:0060089 molecular transducer activity 4 GO:0098772 molecular function regulator activity 2
Localization
GO:0005886 plasma membrane 4 GO:0005783 endoplasmic reticulum 3
Pathway
R-HSA-162582 Signal Transduction 5 R-HSA-112316 Neuronal System 4 R-HSA-9709957 Sensory Perception 2
Partners
ELFN1ELFN2GNAO1GPR179NYXRGS11RGS7TRPM1
Complex memberships
mGluR6 homodimermGluR6–TRPM1–nyctalopin signalosome

Evidence

Reading pass · 27 per-paper findings extracted from the source corpus
Year Finding Method Journal Conf PMIDs
1993 mGluR6 is a metabotropic glutamate receptor that inhibits forskolin-stimulated cyclic AMP accumulation via a G protein-coupled mechanism, with highest agonist selectivity for L-AP4 and L-serine-O-phosphate (one order of magnitude more potent than L-glutamate), and is expressed exclusively in the inner nuclear layer of the retina where ON-bipolar cells reside. cDNA cloning, heterologous expression in CHO cells, cAMP assay, in situ hybridization The Journal of biological chemistry High 8389366
1995 mGluR6 is essential for ON-pathway synaptic transmission from photoreceptors to ON bipolar cells; knockout mice lose ON responses but retain OFF responses, with no change in retinal cell organization or optic fiber projection. Gene targeting (knockout mice), electroretinography, visual behavioral testing Cell High 7889569
1999 mGluR6 signals through G(o) (Gαo), not through a cGMP phosphodiesterase pathway, to close the cation channel in ON bipolar cells; dialysis with Goα suppressed cation current and occluded glutamate response, while anti-Goα antibody reduced the response. Whole-cell patch clamp recordings, intracellular dialysis with G-protein subunits and antibodies, non-hydrolyzable cGMP analogs, PDE inhibitor IBMX The Journal of neuroscience High 10191311
2000 mGluR6 protein is localized to the base of the central element of the postsynaptic triad (400–800 nm from vesicle release sites) in rod and cone ON bipolar cell dendrites of monkey, cat, and rabbit retina; all ON bipolar cell types including ON S-cone bipolar cells express a single mGluR6 isoform. Immunostaining with C-terminus-selective antibody, confocal and electron microscopy The Journal of comparative neurology High 10870081
2000 The mGluR6-gated cation channel in ON bipolar cells is regulated by intracellular Ca2+; Ca2+ influx through the cation channel (which is Ca2+-permeable) causes run-down of the glutamate response by downregulating cation channel function, providing an adaptive mechanism. Whole-cell patch clamp in salamander retinal slices, Ca2+ chelation with BAPTA/EGTA, Ca2+-free bath solution, current-voltage measurements The Journal of neuroscience High 10844016
2002 Ca2+-dependent depression of the mGluR6-mediated glutamate response in ON bipolar cells requires activation of calcineurin (Ca2+/calmodulin-regulated phosphatase); calcineurin acts by reducing the cation channel current, and a constitutively active calcineurin mimics this effect even without Ca2+ elevation. Whole-cell patch clamp, intracellular dialysis with calcineurin inhibitors and constitutively active calcineurin (CaN420), BAPTA buffering Journal of neurophysiology High 12205131
2004 The mGluR6 transduction current in ON bipolar cells desensitizes in a Ca2+-dependent manner; Ca2+ entry through the transduction channel triggers rapid desensitization with a time constant of ~1 s, contributing to conversion of sustained to transient light responses. Whole-cell patch clamp in salamander retinal slices, Ca2+ chelators (EGTA, BAPTA), voltage-jump protocols, mGluR6 agonist/antagonist application The Journal of physiology High 15146044
2006 mGluR6 couples preferentially to Gαo (G(oa) > G(ob), G(i1) > G(i2), G(i3)); no coupling to Gαz or transducin subunits was detected; single-cell RT-PCR confirms Gαo is the only relevant G protein expressed in ON bipolar cells. G-protein reconstitution system in PTX-treated sympathetic neurons, PTX-insensitive Gα mutants, single-cell RT-PCR Visual neuroscience High 17266783
2007 Gbeta5-RGS7 and Gbeta5-RGS11 complexes co-localize with mGluR6 at ON bipolar cell dendritic tips; in mGluR6-deficient mice, these complexes shift away from dendritic tips, indicating that mGluR6 is required for their postsynaptic localization. Immunofluorescence, co-immunoprecipitation, mGluR6 knockout mice, dissociated bipolar cell preparation The European journal of neuroscience High 18001285
2008 A point mutation in mGluR6 (E775K, equivalent to E781K in humans) associated with CSNB1 causes a switch in G-protein coupling: loss of Goα coupling with retention of Gi coupling, while four other CSNB1 mutants show trafficking impairment. Heterologous expression, G-protein coupling assays, trafficking assays in sympathetic neurons Molecular pharmacology Medium 19666700
2009 RGS11 forms an obligatory trimeric complex with Gβ5 (short isoform) and R9AP, localizes to ON bipolar dendritic tips via direct association with mGluR6, and both R9AP and mGluR6 contribute to proteolytic stabilization of the complex; postsynaptic targeting is not determined by R9AP alone. Co-immunoprecipitation, immunofluorescence in KO mice, electrophysiological recordings of light responses in rod ON bipolar cells The Journal of neuroscience High 19625520
2009 TRPM1 long form (TRPM1-L) is the cation channel downstream of mGluR6 in ON bipolar cells; TRPM1-L localizes to dendritic tips co-localized with mGluR6, functions as a constitutively active nonselective cation channel, and its activity is negatively regulated by Goα in the mGluR6 cascade. TRPM1 null mice (ERG, electrophysiology), immunolocalization, heterologous expression with Go Proceedings of the National Academy of Sciences High 19966281
2009 R9AP potentiates the GTPase-accelerating protein (GAP) activity of the RGS11×Gβ5 complex on Gαo by co-localizing them on the membrane and allosterically potentiating GAP function; reconstitution in Xenopus oocytes shows that RGS11×Gβ5-mediated GTPase acceleration of mGluR6-Gαo signaling requires R9AP co-expression. Single-turnover GTPase assays, reconstitution in Xenopus oocytes, in vitro GAP activity assays The Journal of biological chemistry High 20007977
2011 Nyctalopin interacts with both TRPM1 and mGluR6; disruption of mGluR6 prevents targeting of TRPM1 to the postsynaptic compartment of ON bipolar neurons, revealing a macromolecular scaffold where nyctalopin organizes mGluR6 cascade components. Proteomic screen (mass spectrometry), co-immunoprecipitation, mGluR6 KO mice immunohistochemistry The Journal of neuroscience High 21832182
2011 Deletion of mGluR6 renders TRPM1 channels inactive in rod bipolar cells; TRPM1 immunostaining is greatly reduced at dendritic tips (but present in soma/primary dendrites); capsaicin-evoked TRPM1 currents are absent in mGluR6-null cells, suggesting TRPM1 requires the mGluR6 complex to achieve its constitutively active state. Patch clamp electrophysiology, capsaicin application, immunostaining in mGluR6-null mice Journal of neurophysiology High 22131384
2014 GPR179 is required for high sensitivity of the mGluR6 signaling cascade; GPR179 recruits RGS7 and RGS11 to DBC dendritic tips and directly interacts with TRPM1 to alter its gating by capsaicin, independently of the RGS proteins. Gpr179(nob5) mouse ERG, pharmacological gating of TRPM1, noise analysis, comparison with RGS7/RGS11 double KO The Journal of neuroscience High 24790204
2014 Cacna1s (L-type VDCC α1 subunit) localizes to ON bipolar dendritic tips as part of the mGluR6 complex; its localization requires expression of mGluR6 and other cascade components (Gnao1, Gnb3, Gng13, Trpm1), and mGluR6 expression developmentally precedes Cacna1s. PCR, Western blot, immunostaining in multiple KO mice (Grm6, Gnao1, Gnb3, Gng13, Trpm1) Investigative ophthalmology & visual science Medium 24519419
2016 Deletion of Gαo1 greatly reduces dendritic tip staining for Gβ3, Gγ13, Gβ5, RGS11, RGS7, and R9AP but not mGluR6, TRPM1, or PCP2; mGluR6, Gαo1, and Gβ3 deletion all reduce matrix-associated proteins (pikachurin, dystroglycan, dystrophin) presynaptically, suggesting a retrograde trans-synaptic effect mediated through the mGluR6 macromolecular complex. Quantitative immunostaining in Gαo1, mGluR6, Gβ3 KO mice; dendritic invagination counting by electron microscopy The European journal of neuroscience Medium 27037829
2020 The mGluR6 C-terminal domain (CTD) contains ER retention motifs (cluster of basic amino acids); removal of these residues by alanine substitution rescues surface expression of otherwise ER-retained truncation mutants; the CTD is required for cell surface localization and G-protein coupling. Immunocytochemistry, surface biotinylation assays, electrophysiology in 293T cells and hippocampal neurons, site-directed mutagenesis Journal of neurochemistry Medium 33067823
2021 The mGluR6 ligand-binding domain (LBD), but not the C-terminal domain, is required for synaptic localization in ON bipolar cells and for ELFN1 binding in vitro; the C-terminus is dispensable for dendritic tip targeting but is required for TRPM1 trafficking/rescue in mGluR6-null mice. LBD deletion mutants expressed via AAV in mGluR6 null mice, in vitro pulldown for ELFN1 binding, immunohistochemistry, heterologous cell surface localization assays The Journal of biological chemistry High 34793838
2023 Basic residues in the mGluR6 CTD function as ER retention signals; mutations at these residues prevent surface expression even when co-expressed with surface-expressible mGluR6, and surface-deficient mutants reduce surface levels of co-expressed wild-type mGluR6 via heteromeric complex formation. Immunocytochemistry, flow cytometry, immunoprecipitation, site-directed mutagenesis in 293T cells Molecular and cellular neurosciences Medium 37352898
2024 Complex N-glycosylation of mGluR6 (acquired in the Golgi) is required for trans-synaptic interaction with ELFN1 and ELFN2; ELFN proteins bind exclusively to the complex-glycosylated form; mutation at N445 severely impairs ELFN1/2 binding; glycosylation at N445 alone is sufficient for dendritic tip localization, while the quadruple N-glycosylation mutant is completely mislocalized. Glycosidase treatment (PNGase F, Endo H), pulldown with ELFN1/2 extracellular domains, N-glycosylation site mutagenesis, heterologous surface expression, immunohistochemistry in rod bipolar cells The Journal of biological chemistry High 38428819
2024 Multiple CSNB-associated missense mutations in the extracellular ligand-binding domain of mGluR6 cause a trafficking defect: lack of complex N-glycosylation (Golgi bypass) despite efficient plasma membrane insertion; these mutants fail to bind ELFN1 and are mislocalized in bipolar cells. Glycosidase assays, ELFN1 pulldown, immunolocalization in bipolar cells, heterologous expression of patient mutations Life science alliance High 39681475
2025 Trans-synaptic interaction between mGluR6 (postsynaptic) and ELFN1 (presynaptic) is bidirectional: in mGluR6-null mice, presynaptic ELFN1 is partially mislocalized within rod spherules; re-expression of mGluR6 in ON bipolar cells rescues ELFN1 localization; the LRR and LRRCT regions of ELFN1 extracellular domain are necessary and sufficient for binding to mGluR6 and other Group 3 mGluRs. In vitro binding experiments, mGluR6 null mice with AAV rescue, immunofluorescence, ELFN1 domain deletion mutants expressed in rods The Journal of neuroscience High 40930976
2026 CryoEM structure of agonist-bound mGlu6 reveals an asymmetric homodimer arrangement without G protein, indicating agonist binding alone induces receptor asymmetry and pre-organizes the TM domain dimer interface for Gαo binding; a noncanonical interface between the cysteine-rich domain and extracellular loop 2 stabilizes the activation state; mutational analysis shows this interface is required for rapid Gαo activation and surface targeting. CryoEM structure determination, mutagenesis, functional assays for Gαo coupling and surface trafficking Nature communications High 41803130
2025 The upper lobe of the mGluR6 ligand-binding domain regulates secretory trafficking: small deletions in this region cause exclusive unconventional secretion (Golgi bypass) with plasma membrane insertion of immature core-glycosylated protein; larger deletions partially restore Golgi trafficking, suggesting the upper lobe structure is required for ER-to-Golgi sorting. Glycosidase assays, heterologous expression with deletion mutants, surface biotinylation, internalization assays Molecular and cellular neurosciences Medium 41448371
1998 Light-induced CREB phosphorylation and c-fos expression in rod bipolar cells requires mGluR6; these transcriptional responses to both steady and flashing light are absent in mGluR6-deficient mice, and are associated with PKCα-positive rod bipolar cells but not CaM kinase IV. Immunohistochemistry for PCREB and c-fos in mGluR6 KO mice, light stimulation paradigms Brain research. Molecular brain research Medium 9675422

Source papers

Stage 0 corpus · 71 papers · ranked by NIH iCite citations
Year Title Journal Citations PMID
1993 Molecular characterization of a novel retinal metabotropic glutamate receptor mGluR6 with a high agonist selectivity for L-2-amino-4-phosphonobutyrate. The Journal of biological chemistry 603 8389366
1995 Specific deficit of the ON response in visual transmission by targeted disruption of the mGluR6 gene. Cell 409 7889569
2009 TRPM1 is a component of the retinal ON bipolar cell transduction channel in the mGluR6 cascade. Proceedings of the National Academy of Sciences of the United States of America 246 19966281
2005 Night blindness and abnormal cone electroretinogram ON responses in patients with mutations in the GRM6 gene encoding mGluR6. Proceedings of the National Academy of Sciences of the United States of America 199 15781871
2000 Localization of mGluR6 to dendrites of ON bipolar cells in primate retina. The Journal of comparative neurology 163 10870081
2015 Restoring the ON Switch in Blind Retinas: Opto-mGluR6, a Next-Generation, Cell-Tailored Optogenetic Tool. PLoS biology 161 25950461
2005 Mutations in GRM6 cause autosomal recessive congenital stationary night blindness with a distinctive scotopic 15-Hz flicker electroretinogram. Investigative ophthalmology & visual science 125 16249515
1999 The metabotropic receptor mGluR6 may signal through G(o), but not phosphodiesterase, in retinal bipolar cells. The Journal of neuroscience : the official journal of the Society for Neuroscience 122 10191311
1997 ON cone bipolar cells in rat express the metabotropic receptor mGluR6. Visual neuroscience 112 9279006
2010 TRPM1: the endpoint of the mGluR6 signal transduction cascade in retinal ON-bipolar cells. BioEssays : news and reviews in molecular, cellular and developmental biology 93 20544736
2008 Effects of presynaptic mutations on a postsynaptic Cacna1s calcium channel colocalized with mGluR6 at mouse photoreceptor ribbon synapses. Investigative ophthalmology & visual science 92 18952919
2011 TRPM1 forms complexes with nyctalopin in vivo and accumulates in postsynaptic compartment of ON-bipolar neurons in mGluR6-dependent manner. The Journal of neuroscience : the official journal of the Society for Neuroscience 81 21832182
2009 Retina-specific GTPase accelerator RGS11/G beta 5S/R9AP is a constitutive heterotrimer selectively targeted to mGluR6 in ON-bipolar neurons. The Journal of neuroscience : the official journal of the Society for Neuroscience 76 19625520
1997 The mGluR6 5' upstream transgene sequence directs a cell-specific and developmentally regulated expression in retinal rod and ON-type cone bipolar cells. The Journal of neuroscience : the official journal of the Society for Neuroscience 68 9096137
2008 Allelic variance between GRM6 mutants, Grm6nob3 and Grm6nob4 results in differences in retinal ganglion cell visual responses. The Journal of physiology 66 18687716
2007 Generation, identification and functional characterization of the nob4 mutation of Grm6 in the mouse. Visual neuroscience 61 17430614
1994 Expression of mRNAs of L-AP4-sensitive metabotropic glutamate receptors (mGluR4, mGluR6, mGluR7) in the rat retina. Neuroscience letters 60 8084499
2007 Gbeta5-RGS complexes co-localize with mGluR6 in retinal ON-bipolar cells. The European journal of neuroscience 59 18001285
2000 Regulation of the on bipolar cell mGluR6 pathway by Ca2+. The Journal of neuroscience : the official journal of the Society for Neuroscience 59 10844016
2014 GPR179 is required for high sensitivity of the mGluR6 signaling cascade in depolarizing bipolar cells. The Journal of neuroscience : the official journal of the Society for Neuroscience 56 24790204
2007 A novel connection between rods and ON cone bipolar cells revealed by ectopic metabotropic glutamate receptor 7 (mGluR7) in mGluR6-deficient mouse retinas. The Journal of neuroscience : the official journal of the Society for Neuroscience 54 17553999
2011 mGluR6 deletion renders the TRPM1 channel in retina inactive. Journal of neurophysiology 52 22131384
2016 AAV-mediated transduction and targeting of retinal bipolar cells with improved mGluR6 promoters in rodents and primates. Gene therapy 49 27115727
1997 Impairment of pupillary responses and optokinetic nystagmus in the mGluR6-deficient mouse. Neuropharmacology 48 9144650
1997 (S)-homo-AMPA, a specific agonist at the mGlu6 subtype of metabotropic glutamic acid receptors. Journal of medicinal chemistry 45 9357538
1997 Cloning, distribution and functional expression of the human mGlu6 metabotropic glutamate receptor. Neuropharmacology 40 9144651
2004 Desensitization of the mGluR6 transduction current in tiger salamander On bipolar cells. The Journal of physiology 36 15146044
2011 A phenotypic study of congenital stationary night blindness (CSNB) associated with mutations in the GRM6 gene. Acta ophthalmologica 33 22008250
2009 Sequence variations of GRM6 in patients with high myopia. Molecular vision 26 19862333
2002 Regulation of the retinal bipolar cell mGluR6 pathway by calcineurin. Journal of neurophysiology 24 12205131
2010 Response to methadone maintenance treatment is associated with the MYOCD and GRM6 genes. Molecular diagnosis & therapy 23 20560679
2008 Photopic electroretinograms of mGluR6-deficient mice. Current eye research 22 18214746
2009 Isolation of ON bipolar cell genes via hrGFP-coupled cell enrichment using the mGluR6 promoter. Journal of biochemistry 21 19270057
2009 Membrane anchor R9AP potentiates GTPase-accelerating protein activity of RGS11 x Gbeta5 complex and accelerates inactivation of the mGluR6-G(o) signaling. The Journal of biological chemistry 21 20007977
2014 Localization of Cacna1s to ON bipolar dendritic tips requires mGluR6-related cascade elements. Investigative ophthalmology & visual science 19 24519419
2011 mGluR6 transcripts in non-neuronal tissues. The journal of histochemistry and cytochemistry : official journal of the Histochemistry Society 19 22034516
1997 A late ON response remains in visual response of the mGluR6-deficient mouse. Neuroscience letters 19 9350851
2006 G protein coupling profile of mGluR6 and expression of G alpha proteins in retinal ON bipolar cells. Visual neuroscience 18 17266783
2021 The mGluR6 ligand-binding domain, but not the C-terminal domain, is required for synaptic localization in retinal ON-bipolar cells. The Journal of biological chemistry 17 34793838
2015 Identification of a new mutant allele, Grm6(nob7), for complete congenital stationary night blindness. Visual neuroscience 17 26241901
1998 CREB-induced transcriptional activation depends on mGluR6 in rod bipolar cells. Brain research. Molecular brain research 16 9675422
2021 Restoration of mGluR6 Localization Following AAV-Mediated Delivery in a Mouse Model of Congenital Stationary Night Blindness. Investigative ophthalmology & visual science 14 33729473
2020 Whole-genome sequencing identifies missense mutation in GRM6 as the likely cause of congenital stationary night blindness in a Tennessee Walking Horse. Equine veterinary journal 14 32654228
2018 Different Activity Patterns in Retinal Ganglion Cells of TRPM1 and mGluR6 Knockout Mice. BioMed research international 14 29854741
2017 A missense mutation in Grm6 reduces but does not eliminate mGluR6 expression or rod depolarizing bipolar cell function. Journal of neurophysiology 14 28490646
2014 Effects of mGluR6-deficiency on photoreceptor ribbon synapse formation: comparison of electron microscopic analysis of serial sections with random sections. Visual neuroscience 14 24801622
2016 Lack of mGluR6-related cascade elements leads to retrograde trans-synaptic effects on rod photoreceptor synapses via matrix-associated proteins. The European journal of neuroscience 13 27037829
2009 Altered G-protein coupling in an mGluR6 point mutant associated with congenital stationary night blindness. Molecular pharmacology 13 19666700
2001 Alternative splicing of mGlu6 gene generates a truncated glutamate receptor in rat retina. Neuroreport 11 11522953
2012 Mutation screening of TRPM1, GRM6, NYX and CACNA1F genes in patients with congenital stationary night blindness. International journal of molecular medicine 10 22735794
2019 Pseudodominant inheritance of autosomal recessive congenital stationary night blindness in one family with three co-segregating deleterious GRM6 variants identified by next-generation sequencing. Molecular genetics & genomic medicine 9 31677249
2008 The mGlu(4) receptor allosteric modulator N-phenyl-7-(hydroxyimino)cyclopropa[b]chromen-1a-carboxamide acts as a direct agonist at mGlu(6) receptors. European journal of pharmacology 9 18593581
2024 Complex N-glycosylation of mGluR6 is required for trans-synaptic interaction with ELFN adhesion proteins. The Journal of biological chemistry 8 38428819
2021 Optogenetic control of neural differentiation in Opto-mGluR6 engineered retinal pigment epithelial cell line and mesenchymal stem cells. Journal of cellular biochemistry 8 33847009
2018 Impacts of GRIN3A, GRM6 and TPH2 genetic polymorphisms on quality of life in methadone maintenance therapy population. PloS one 8 30059533
2015 Mutations in GRM6 identified in consanguineous Pakistani families with congenital stationary night blindness. Molecular vision 8 26628857
2020 Involvement of the C-terminal domain in cell surface localization and G-protein coupling of mGluR6. Journal of neurochemistry 7 33067823
2023 Additional evidence supports GRM6 p.Thr178Met as a cause of congenital stationary night blindness in three horse breeds. Veterinary ophthalmology 6 37815029
2024 Defective glycosylation and ELFN1 binding of mGluR6 congenital stationary night blindness mutants. Life science alliance 4 39681475
2014 [Association of ZNF644, GRM6 and CTNND2 genes polymorphisms with high myopia]. Zhonghua yi xue za zhi 4 25142846
2019 Reduced expression of the nob8 gene does not normalize the distribution or function of mGluR6 in the mouse retina. Molecular vision 3 32025181
2024 Compound heterozygous mutations in GRM6 causing complete Schubert-Bornschein type congenital stationary night blindness. Heliyon 2 38434377
2024 Engineered red Opto-mGluR6 Opsins, a red-shifted optogenetic excitation tool, an in vitro study. PloS one 1 39446870
2024 Differential Localization and Functional Roles of mGluR6 Paralogs in Zebrafish Retina. Investigative ophthalmology & visual science 1 39475940
2023 The intracellular C-terminal domain of mGluR6 contains ER retention motifs. Molecular and cellular neurosciences 1 37352898
2019 Effect and mechanism of mGluR6 on the biological function of rat embryonic neural stem cells. Bioscience, biotechnology, and biochemistry 1 30739574
2026 CryoEM structure of mGlu6 captures receptor activation prior to G protein coupling. Nature communications 0 41803130
2025 Novel Grm6 Variant in a no b-wave (nob) Mouse Model: Phenotype Characterization and Gene Therapy. Investigative ophthalmology & visual science 0 40923695
2025 Trans-synaptic Interaction with mGluR6 Contributes to ELFN1 Presynaptic Enrichment in Rod Photoreceptors. The Journal of neuroscience : the official journal of the Society for Neuroscience 0 40930976
2025 The extracellular domain of mGluR6 regulates targeting to the conventional secretion pathway. Molecular and cellular neurosciences 0 41448371
2025 System biology analysis reveals that Grm6 is associated with glutamate accumulation-induced scotopic vision impairment in diabetic mice. Molecular vision 0 41867370