Affinage

GRM5

Metabotropic glutamate receptor 5 · UniProt P41594

Length
1212 aa
Mass
132.5 kDa
Annotated
2026-06-10
100 papers in source corpus 32 papers cited in narrative 32 extracted findings
Cross-family judge vs UniProt: Affinage preferred faithfulness: 6/6 claims corpus-supported (100%)

Mechanistic narrative

Synthesis pass · prose summary of the discoveries below

GRM5 (mGluR5) is a dimeric class C G-protein-coupled receptor that couples to Gq/phospholipase C to drive phosphoinositide hydrolysis and IP3-dependent Ca2+ mobilization, and is the principal group I metabotropic glutamate receptor controlling synaptic plasticity, sensory processing, and glial-neuronal signaling (PMID:7636025, PMID:9202306, PMID:39209876). The receptor is concentrated postsynaptically on dendritic spines and shafts with presynaptic axon-terminal expression, and it acts as a perisynaptic autoreceptor whose C-terminal domain confines it to nanodomains adjacent to but excluded from the synapse, a localization that gates synaptic Ca2+ responses (PMID:7636025, PMID:18625255, PMID:36646691). Activation of mGluR5 produces ERK, CaMK, and CREB signaling and is sufficient to induce protein-synthesis-dependent mGluR-LTD in hippocampal CA1 distinct from NMDAR-dependent LTD, while genetic loss impairs spatial learning and fear conditioning (PMID:11431513, PMID:11566212, PMID:19840937). mGluR5 signals from both the plasma membrane and intracellular ER/nuclear membranes; the intracellular pool is supplied with glutamate by the transporter EAAT3 and selectively drives sustained Ca2+ rises, ERK1/2-Elk-1 signaling, immediate-early gene induction, and LTD, and underlies neuropathic pain behaviors (PMID:19840937, PMID:24672004, PMID:26837579). Its surface availability and trafficking are tightly regulated: it internalizes constitutively via a clathrin-independent, dynamin-2-dependent route with recycling to the surface (PMID:12529370, PMID:22995293); PKC phosphorylation at Ser901 displaces calmodulin to favor Siah-1A binding and lysosomal degradation (PMID:23152621); and p11/S100A10 binding to the cytoplasmic tail and NHERF-2 PDZ interaction promote surface expression and prolong Ca2+ signaling, respectively (PMID:16891310, PMID:26370144). mGluR5 is embedded in a wider receptor and scaffold network—forming Gq-coupled heteromers with D1 dopamine receptors, synergizing with adenosine A2A receptors to potentiate DARPP-32 phosphorylation, cooperating with CB1 receptors for neuroprotection, and engaging Homer scaffolds to drive mTOR-dependent AMPA receptor plasticity (PMID:12538871, PMID:27543109, PMID:31420117, PMID:32039920). It links to translational control through FMRP, releasing FMRP repression of APP mRNA upon activation (PMID:17298186), and astrocytic mGluR5 transiently re-emerging after injury drives synaptogenesis and allodynia (PMID:35319723). Aberrant mGluR5 signaling contributes to L-DOPA-induced dyskinesia via upregulated D1-mGlu5 nanocomplexes (PMID:32039920) and to Alzheimer's disease synaptic loss via Abeta-oligomer-driven aberrant signaling that allosteric modulators can normalize (PMID:35648810), and pathogenic anti-mGluR5 IgG antibodies cause receptor internalization in encephalitis (PMID:29703767).

Mechanistic history

Synthesis pass · year-by-year structured walk · 22 steps
  1. 1995 High

    Established mGluR5 as a Gq-coupled receptor driving phosphoinositide hydrolysis and Ca2+ mobilization and mapped its predominantly postsynaptic, partly presynaptic and astroglial distribution, defining where it acts.

    Evidence Receptor-specific Western blot, immunocytochemistry, and immunoelectron microscopy in rat brain with transfection of nonneuronal cells

    PMID:7636025 PMID:8576426

    Open questions at the time
    • Did not resolve functional differences between presynaptic and postsynaptic pools
    • Coupling partners beyond PI hydrolysis not addressed
  2. 1997 High

    Showed in native astrocytes that mGluR5 activation drives PI hydrolysis without cAMP and undergoes two-phase desensitization, distinguishing a phosphorylation-independent early phase from protein-synthesis-dependent resensitization.

    Evidence Pharmacological PI hydrolysis and cAMP assays with phorbol esters and down-regulation assays in cultured astrocytes

    PMID:9202306

    Open questions at the time
    • Molecular mediators of early desensitization not identified
    • In vivo relevance not tested
  3. 2001 High

    Defined mGluR5 as both necessary and sufficient for protein-synthesis-dependent hippocampal LTD and for spatial/contextual memory, separating it mechanistically from NMDAR-dependent plasticity.

    Evidence Hippocampal slice electrophysiology with selective DHPG/antagonists and protein synthesis inhibitors; mGluR5 knockout mice in Morris water maze and fear conditioning

    PMID:11431513 PMID:11566212

    Open questions at the time
    • Downstream PKC/Src pathway to memory was inferred not directly demonstrated
    • Subcellular site of LTD induction unresolved at this stage
  4. 2001 High

    Identified a peripheral pro-nociceptive role for mGluR5 on primary afferent terminals, localizing analgesic relevance to the periphery.

    Evidence Intraplantar/i.c.v./intrathecal MPEP, behavioral pain testing, dorsal-horn neuron recordings, and mGluR5/TRPV1 co-labeling

    PMID:11077066

    Open questions at the time
    • Intracellular signaling linking peripheral mGluR5 to hyperalgesia not defined here
  5. 2003 High

    Revealed mGluR5 endocytoses constitutively through a clathrin-independent, dynamin-2-dependent route, redefining its trafficking distinct from canonical GPCR pathways.

    Evidence Imaging and biochemical endocytosis assays with dominant-negative Eps15 and dynamin-2 in COS-7 cells and neurons

    PMID:12529370

    Open questions at the time
    • Post-endocytic fate (recycling vs degradation) not fully resolved
    • Adaptor proteins for the clathrin-independent route unknown
  6. 2003 High

    Showed mGluR5 cross-talks with adenosine A2A receptors to potentiate DARPP-32 phosphorylation via cAMP/ERK independently of PLC, establishing receptor synergy in striatum.

    Evidence Neostriatal slice pharmacology with receptor antagonists and kinase inhibitors, DARPP-32 phospho-assays

    PMID:12538871

    Open questions at the time
    • Physical basis of mGluR5-A2A interaction not defined
    • In vivo behavioral consequence not tested here
  7. 2004 Medium

    Demonstrated bidirectional mGluR5 control of NMDAR responses—Ca2+/PKC-dependent inhibition versus tonic tyrosine-kinase-dependent potentiation—revealing context-dependent crosstalk.

    Evidence Ca2+ imaging in HEK293 cells co-expressing NMDAR subunits with thapsigargin, PKC, PTK, and PTP inhibitors

    PMID:15210575

    Open questions at the time
    • Heterologous cells only
    • Native neuronal validation absent
  8. 2006 High

    Identified NHERF-2 as a selective C-terminal PDZ partner of mGluR5 that prolongs Ca2+ signaling and potentiates excitotoxicity, linking scaffolding to signal duration.

    Evidence PDZ array screen, reverse overlay, point mutagenesis, reciprocal co-IP, calcium and cell-death assays

    PMID:16891310

    Open questions at the time
    • Physiological cell-death relevance in vivo not established
    • Interplay with other C-terminal partners not addressed
  9. 2007 High

    Connected mGluR5 to translational control by showing activation releases FMRP repression of APP mRNA, linking the receptor to local protein synthesis and Abeta production.

    Evidence RNA-protein binding, FMRP-APP mRNA co-IP, DHPG stimulation of synaptoneurosomes, fmr-1 KO comparison, Abeta ELISA

    PMID:17298186

    Open questions at the time
    • Signaling steps from mGluR5 to FMRP release not mapped
    • In vivo APP/Abeta consequences not quantified
  10. 2008 High

    Confirmed mGluR5 functions as a bona fide presynaptic autoreceptor facilitating glutamate exocytosis, using genetic deletion to validate concentration-dependent pharmacology.

    Evidence Synaptosome [3H]D-aspartate release with selective antagonists and mGluR5 knockout, subsynaptic fractionation

    PMID:18625255

    Open questions at the time
    • Presynaptic signaling cascade not dissected
  11. 2009 High

    Discovered that surface versus intracellular mGluR5 pools generate distinct Ca2+ signatures and signaling outputs, with intracellular receptor uniquely driving ERK/Elk-1 and immediate-early genes.

    Evidence Cell-permeable vs impermeable ligand isolation, Ca2+ imaging, phospho-protein and gene-expression assays with kinase inhibitors

    PMID:19840937

    Open questions at the time
    • Source of intracellular ligand not yet identified at this stage
    • Native tissue confirmation pending
  12. 2012 High

    Defined the regulatory switch by which PKC phosphorylation at Ser901 displaces calmodulin to favor Siah-1A binding, routing mGluR5 to lysosomal degradation, while a parallel study established constitutive recycling in heterologous cells.

    Evidence Co-IP, S901 mutagenesis, surface biotinylation, and lysosomal/recycling trafficking assays in neurons and HEK293 cells

    PMID:22995293 PMID:23152621

    Open questions at the time
    • Conditions selecting recycling versus degradation in vivo not defined
    • Kinetics of CaM/Siah-1A competition unresolved
  13. 2014 High

    Localized intracellular mGluR5 to ER/nuclear membranes supplied with glutamate by EAAT3 and showed it selectively mediates LTD but not LTP, providing the missing source for intracellular activation.

    Evidence Cell-permeable/impermeable ligand isolation, radiolabeled agonist uptake, EAAT3 inhibition, Ca2+ imaging, hippocampal slice electrophysiology

    PMID:24672004

    Open questions at the time
    • Mechanism targeting receptor to intracellular membranes unclear
    • Relative contribution of surface vs intracellular pool to physiological LTD unsettled
  14. 2015 High

    Established p11/S100A10 as a tail-binding partner promoting mGluR5 surface expression and Ca2+ signaling with opposing behavioral effects in glutamatergic versus GABAergic neurons, and showed biased PAMs can separate Gq signaling from NMDAR modulation in vivo.

    Evidence Co-IP, surface biotinylation, calcium assays, cell-type-specific conditional KO and behavior; biased PAM electrophysiology, signaling, and behavioral models

    PMID:25937172 PMID:26370144

    Open questions at the time
    • Structural basis of biased PAM signaling not resolved
    • How p11 directs receptor trafficking mechanistically unclear
  15. 2016 High

    Extended intracellular mGluR5 biology to spinal nociception—nuclear-membrane receptor driving sustained Ca2+ and pERK/Arc/c-fos underlies neuropathic pain—and identified cooperative mGluR5-CB1 neuroprotection via MEK/ERK and PI3K/AKT.

    Evidence Subcellular fractionation, Ca2+ imaging, intrathecal cell-permeable/impermeable antagonists, EAAT-3 inhibition, behavior; primary neuron receptor blockade/ablation with kinase inhibitors

    PMID:26837579 PMID:27543109

    Open questions at the time
    • Physical mGluR5-CB1 association not demonstrated
    • Neuroprotection mechanism is correlative for some signaling steps
  16. 2017 Medium

    Broadened mGluR5 roles to peripheral TRP channel sensitization via PKCepsilon, immune RANTES/NF-kB signaling in T cells, and epigenetic (Tet1-dependent) transcriptional control of the mGluR5 promoter.

    Evidence In vivo pain behavior with peripheral pharmacology and PKCepsilon assays; Jurkat T-cell agonist/antagonist with NF-kB reporter; intrathecal Tet1 gene transfer with ChIP and bisulfite sequencing

    PMID:28621704 PMID:28718992 PMID:29849049

    Open questions at the time
    • T-cell findings rest on a single cell line
    • Pain pathways established pharmacologically rather than biochemically
    • Generality of Tet1-mGluR5 epigenetic regulation beyond pain unknown
  17. 2018 Medium

    Linked mGluR5 dysregulation to human disease—pathogenic anti-mGluR5 IgG internalizes surface receptor in encephalitis, and schizophrenia DLPFC shows reduced Gq/Homer/PI3K coupling with hyperphosphorylation and altered scaffold interactions.

    Evidence Patient IgG application to neurons with receptor cluster quantification; co-IP of mGluR5 with Gq/11, Homer, PI3K, GluN, RGS4, Norbin, Preso1, Tamalin and phospho-assays in postmortem tissue

    PMID:29703767 PMID:30214040

    Open questions at the time
    • Postmortem associations are correlative
    • Causal direction of phosphorylation changes in disease unresolved
    • Single methodological approach for antibody pathogenicity
  18. 2019 High

    Showed Homer1a-enhanced mGluR5 signaling drives mTOR-dependent AMPA receptor potentiation underlying rapid antidepressant action, requiring mGluR5 specifically in CaMK2a excitatory neurons.

    Evidence TAT-Homer1a peptide, conditional mGluR5 KO in CaMK2a neurons, electrophysiology, mTOR phospho-assays, AMPAR surface assays, antidepressant behavior

    PMID:31420117

    Open questions at the time
    • Direct structural Homer1a-mGluR5 engagement during this response not resolved
    • Link between mTOR and AMPAR trafficking incompletely defined
  19. 2020 High

    Demonstrated D1-mGluR5 heteromers couple to Gq for synergistic PLC/Ca2+ signaling and are upregulated in dopamine-denervated striatum, driving excessive ERK and dyskinesia.

    Evidence Co-IP, proximity ligation, BRET/FRET, calcium/PLC and ERK assays in rodent Parkinson's models with dyskinesia behavior

    PMID:32039920

    Open questions at the time
    • Stoichiometry and interface of the heteromer not defined
    • Therapeutic targetability of the heteromer untested
  20. 2022 High

    Established astrocytic mGluR5 re-emergence after injury as causally driving synaptogenesis and allodynia, and validated mGluR5 silent allosteric modulation to normalize Abeta-driven synaptotoxic signaling and restore synapses in AD models.

    Evidence Astrocyte-specific mGluR5 KO with Ca2+ imaging, synaptogenic-molecule IHC and behavior; oral SAM BMS-984923 with PET occupancy/synaptic density, single-nuclei transcriptomics, and C1Q/engulfment assays in AD mice

    PMID:35319723 PMID:35648810

    Open questions at the time
    • Signaling cascade from astrocytic mGluR5 to synaptogenic gene expression not fully mapped
    • Translation of SAM efficacy to humans untested in these studies
  21. 2023 High

    Resolved that mGluR5 is dynamically confined to perisynaptic nanodomains by its C-terminal domain, and that forcing synaptic entry acutely boosts synaptic Ca2+, linking nanoscale localization to function.

    Evidence Single-molecule localization microscopy, inducible chemogenetic recruitment, synaptic Ca2+ imaging, and C-terminal mutagenesis

    PMID:36646691

    Open questions at the time
    • Molecular tethers enforcing perisynaptic exclusion not identified
    • Physiological signals that mobilize the receptor to synapses unknown
  22. 2024 Medium

    Provided a stepwise asymmetric allosteric activation model for the dimeric receptor, explaining how agonist-driven ectodomain compaction and PAM-stabilized 7TM interfaces enable G-protein coordination.

    Evidence Markov state models from atomistic MD simulations with experimental signaling validation

    PMID:39209876

    Open questions at the time
    • No experimental high-resolution structure of the activation intermediates
    • Computational mechanism awaits cryo-EM confirmation

Open questions

Synthesis pass · forward-looking unresolved questions
  • How surface versus ER/nuclear mGluR5 pools are differentially targeted, scaffolded, and recruited to perisynaptic nanodomains—and how these spatial states are coordinated to select signaling and plasticity outcomes—remains unresolved.
  • Trafficking determinants directing receptor to intracellular membranes unknown
  • Molecular tethers enforcing perisynaptic confinement unidentified
  • How biased pharmacology maps onto subcellular pools in vivo is undefined

Mechanism profile

Synthesis pass · controlled-vocabulary classification · explore literature graph →
Molecular activity
GO:0060089 molecular transducer activity 3 GO:0098772 molecular function regulator activity 3 GO:0140110 transcription regulator activity 1
Localization
GO:0005886 plasma membrane 4 GO:0005768 endosome 3 GO:0005635 nuclear envelope 2 GO:0005783 endoplasmic reticulum 1
Pathway
R-HSA-112316 Neuronal System 4 R-HSA-162582 Signal Transduction 4 R-HSA-1643685 Disease 3
Partners
ADORA2ACALM1DRD1FMR1HOMER1NHERF2S100A10SIAH1
Complex memberships
D1-mGluR5 heteromer

Evidence

Reading pass · 32 per-paper findings extracted from the source corpus
Year Finding Method Journal Conf PMIDs
1995 mGluR5 is a G-protein coupled receptor that couples to phosphatidylinositol hydrolysis and calcium mobilization via inositol triphosphate. Immunoelectron microscopy in rat brain showed it is predominantly localized on postsynaptic dendritic spines and shafts, with some presynaptic axon terminal labeling, suggesting a presynaptic autoreceptor role in addition to postsynaptic function. Western blot (receptor-specific antibody), immunocytochemistry, electron microscopy, transfection of nonneuronal cells The Journal of comparative neurology High 7636025
1995 mGluR5 protein expression is dramatically higher during early hypothalamic development compared to adults (sixfold decrease in hypothalamus, threefold in cortex with maturation). Ultrastructurally, mGluR5 localizes to the cytoplasmic face of the plasma membrane on hypothalamic dendrites, dendritic spines, and perikarya, and is also expressed on astrocyte processes surrounding asymmetric synapses. Western blot, Northern blot, immunocytochemistry, electron microscopy The Journal of comparative neurology High 8576426
1997 In native astrocytes expressing mGluR5 without mGluR1 interference, mGluR5 activation induces phosphoinositide (PI) hydrolysis without stimulating cAMP formation. Prolonged agonist exposure causes two-phase desensitization: an early phase (completed by 1 h) independent of receptor internalization or PKC/PKA phosphorylation, and a late phase (by 24 h) associated with receptor down-regulation. Resensitization after prolonged exposure requires new protein synthesis. Pharmacological assays (PI hydrolysis, cAMP measurement), phorbol ester treatment, receptor down-regulation assays in cultured astrocytes Journal of neurochemistry High 9202306
2001 Pharmacological activation of mGluR5 (but not mGluR1) by DHPG is sufficient to induce long-term depression (LTD) in hippocampal CA1. This mGluR5-LTD is saturable, mechanistically distinct from NMDAR-dependent LTD, and shares an expression mechanism with protein synthesis-dependent LTD induced by synaptic stimulation. Electrophysiology (field recordings in hippocampal slices), selective pharmacological tools (DHPG, mGluR5 antagonists), protein synthesis inhibitors Journal of neurophysiology High 11431513
2001 mGluR5 expressed on peripheral terminals of primary afferent neurons mediates inflammatory hyperalgesia. Intraplantar but not intracerebroventricular or intrathecal injection of the selective mGluR5 antagonist MPEP reduces Freund's complete adjuvant-induced hind paw hyperalgesia. Group I mGluR agonist-induced mechanical hyperalgesia was blocked by MPEP but not by the mGluR1 antagonist 4-CPG. In vivo pharmacology (intraplantar, i.c.v., intrathecal microinjection), behavioral pain testing, in vivo electrophysiology (dorsal horn WDR neuron recordings), double-label immunohistochemistry (mGluR5 + βIII-tubulin; mGluR5 + TRPV1) Neuropharmacology High 11077066
2001 mGluR5 is required for spatial learning and context-dependent fear conditioning. mGluR5 knockout mice are deficient in Morris water maze performance and contextual fear conditioning, establishing a pathway linking mGluR5 → PKC → Src → enhanced NMDAR open probability → LTP of NMDAR, necessary for spatial memory. Genetic knockout (mGluR5 null mice), Morris water maze, fear conditioning, hippocampal slice electrophysiology (LTP recording) Physiology & behavior Medium 11566212
2003 mGluR5 endocytosis occurs via a clathrin-independent, dynamin-2-dependent pathway. mGluR5a and mGluR5b internalize constitutively in COS-7 cells and neurons (axons and dendrites) even without ligand activation or in the presence of an inverse agonist. Dominant-negative Eps15 (clathrin pathway blocker) does not prevent mGluR5 endocytosis, but dynamin-2 is required. Transfection in COS-7 cells and hippocampal neurons, immunocytochemistry, quantitative image analysis, biochemical endocytosis assay, dominant-negative Eps15 constructs The Journal of biological chemistry High 12529370
2003 mGluR5 potentiates adenosine A2A receptor-mediated DARPP-32 phosphorylation at Thr-34 in neostriatal neurons by stimulating A2A receptor-coupled cAMP formation in an ERK-dependent manner. The action of mGluR5 requires A2A receptor activation by endogenous adenosine. Coactivation of mGluR5 and A2A receptors synergistically increases DARPP-32 phosphorylation. The effect is not dependent on PLC activation. Neostriatal slice pharmacology, DARPP-32 phosphorylation assays, selective receptor antagonists, kinase inhibitors (ERK, PLC, p38, CK1, Cdk5) Proceedings of the National Academy of Sciences of the United States of America High 12538871
2004 mGluR5 expressed in HEK293 cells can both inhibit and potentiate NMDA receptor responses through distinct mechanisms. The inhibitory influence depends on Ca2+ release from stores (thapsigargin-sensitive) and PKC activation. Removal of these processes reveals a tonic mGluR5- and protein tyrosine kinase (PTK)-dependent potentiation of NMDA receptors. Protein tyrosine phosphatase (PTP) inhibitors occlude DHPG-induced NMDAR potentiation. Ca2+ imaging in HEK293 cells co-transfected with NR1a, NR2A, and mGlu5a; pharmacological dissection with thapsigargin, staurosporine, PTK inhibitors (genistein, PP2), PTP inhibitors (orthovanadate, PAO) British journal of pharmacology Medium 15210575
2006 The PDZ scaffold NHERF-2 directly and selectively interacts with mGluR5 (not mGluR1a) via the second PDZ domain of NHERF-2 binding to the C-terminus of mGluR5. A single point mutation in mGluR5-CT completely disrupts this interaction. NHERF-2 co-immunoprecipitates with full-length mGluR5 in cells, and co-expression of NHERF-2 prolongs mGluR5-mediated calcium mobilization and potentiates mGluR5-mediated cell death. PDZ domain proteomic array screening, reverse overlay assay, point mutagenesis, co-immunoprecipitation, confocal microscopy, functional calcium assays, cell death assays, immunohistochemistry in mouse brain The Journal of biological chemistry High 16891310
2007 FMRP binds to the coding region of APP mRNA at a guanine-rich, G-quartet-like sequence. Stimulation of cortical synaptoneurosomes or neurons with the mGluR5 agonist DHPG increases APP translation in wild-type but not fmr-1 knockout samples. APP mRNA co-immunoprecipitates with FMRP in resting synaptoneurosomes, but this interaction is lost shortly after DHPG treatment, indicating that mGluR5 activation releases FMRP repression of APP mRNA translation. RNA-protein binding assays, co-immunoprecipitation (FMRP-APP mRNA), DHPG stimulation of synaptoneurosomes and primary neurons, metabolic labeling, fmr-1 KO mouse comparison, ELISA (Aβ levels) PLoS biology High 17298186
2008 mGluR5 functions as a presynaptic autoreceptor on glutamatergic cortical nerve terminals, facilitating evoked glutamate exocytosis. Low concentrations of DHPG (0.3 μM) potentiate depolarization-evoked [3H]D-aspartate release via mGluR5 (blocked by MPEP, not CPCCOEt), whereas high concentrations (50 μM) act via mGluR1. This mGluR5 presynaptic role was confirmed by absence of potentiation in mGluR5 knockout synaptosome preparations. Synaptosome [3H]D-aspartate release assay, selective pharmacological antagonists (MPEP, CPCCOEt), mGluR5 knockout mice, Western blot of subsynaptic fractions, immunocytochemistry Neuropharmacology High 18625255
2009 Activation of cell surface versus intracellular mGluR5 produces distinct Ca2+ signatures and unique downstream signaling. Both pools activate JNK, CaMK, and CREB phosphorylation; however, only intracellular mGluR5 activates ERK1/2 and Elk-1 phosphorylation, resulting in upregulation of c-fos and egr1 but not c-jun. CaMK kinase mediates CREB phosphorylation downstream of mGluR5, while CaMKII is upstream of intracellular mGluR5-mediated Elk-1 phosphorylation. Intracellular mGluR5 is activated by glutamate transported into the cell. Pharmacological isolation of surface vs. intracellular receptor pools (cell-impermeable vs. cell-permeable ligands), Ca2+ imaging, phospho-protein assays (JNK, CaMK, CREB, ERK1/2, Elk-1), kinase inhibitors, gene expression analysis, genetic approaches The Journal of biological chemistry High 19840937
2012 PKC phosphorylation of mGluR5 at Ser901 enhances binding of the E3 ligase Siah-1A by displacing calmodulin (CaM). Siah-1A binding to mGluR5 decreases receptor surface expression and increases lysosomal degradation via endosomal trafficking. CaM and Siah-1A compete for mGluR5 binding in a phosphorylation-dependent manner in rat hippocampal neurons. Co-immunoprecipitation in hippocampal neurons, site-directed mutagenesis (S901 phosphorylation site), surface biotinylation assay, lysosomal degradation assays The Journal of neuroscience : the official journal of the Society for Neuroscience High 23152621
2012 mGluR5 constitutively internalizes in HEK293 cells in the absence of ligand. Following endocytosis, the receptor enters the recycling compartment and returns to the cell surface; no lysosomal localization is observed after constitutive internalization. Surface biotinylation assays, antibody feeding internalization assay, confocal microscopy with organelle markers in HEK293 cells Biochemical and biophysical research communications Medium 22995293
2014 Intracellular mGluR5 is present on the endoplasmic reticulum and nucleus of hippocampal CA1 neurons, where it colocalizes with the glutamate transporter EAAT3. Inhibition of EAAT3 prevented accumulation of radiolabeled agonist at intracellular mGluR5. Both intracellular and cell surface mGluR5 induced oscillatory Ca2+ responses, but only intracellular mGluR5 triggered sustained high-amplitude Ca2+ rises in dendrites. Activation of intracellular mGluR5 alone mediated both electrically- and chemically-induced LTD but not LTP in acute hippocampal slices. Pharmacological isolation of intracellular vs. surface mGluR5 (cell-permeable vs. impermeable ligands), Ca2+ imaging, radiolabeled agonist uptake assays, EAAT3 inhibition, acute hippocampal slice electrophysiology The Journal of neuroscience : the official journal of the Society for Neuroscience High 24672004
2015 p11 (S100A10) directly binds to the cytoplasmic tail of mGluR5. p11 and mGluR5 mutually facilitate their accumulation at the plasma membrane, and p11 increases cell-surface availability of mGluR5. Overexpression of p11 potentiates mGluR5 agonist-induced calcium responses. Knockout of mGluR5 or p11 specifically in glutamatergic neurons causes depression-like behaviors, while knockout in GABAergic neurons causes antidepressant-like behaviors. Co-immunoprecipitation, cell-surface biotinylation, calcium signaling assays, cell-type-specific conditional knockout (glutamatergic vs. GABAergic neurons), behavioral assays Molecular psychiatry High 26370144
2015 Biased mGluR5 PAMs can selectively potentiate mGluR5 coupling to Gαq-mediated signaling without potentiating mGluR5 modulation of NMDAR currents or NMDAR-dependent synaptic plasticity. VU0409551 produced antipsychotic-like and cognition-enhancing activity in animal models despite not potentiating NMDAR function, demonstrating that NMDAR current modulation is not required for in vivo efficacy of mGluR5 PAMs. Electrophysiology (hippocampal slice NMDAR currents), calcium signaling assays (Gαq), behavioral models (psychosis, cognition), selective PAM pharmacology Neuron High 25937172
2016 In spinal dorsal horn neurons, >80% of mGluR5 is intracellular, with ~60% located on nuclear membranes where activation produces sustained Ca2+ responses. Nerve injury increases nuclear mGluR5 expression and receptor-mediated pERK1/2, Arc/Arg3.1, and c-fos. Spinal blockade of intracellular (but not cell surface) mGluR5 reduces neuropathic pain behaviors. Blocking EAAT-3 to reduce intracellular glutamate mimics the effects of intracellular mGluR5 antagonism. Immunofluorescence/confocal microscopy (subcellular fractionation), Ca2+ imaging, intrathecal drug delivery (cell-impermeable vs. permeable mGluR5 antagonists), EAAT-3 inhibition, behavioral pain testing, Western blot (pERK1/2, Arc, c-fos) Nature communications High 26837579
2016 mGluR5 (postsynaptic) and CB1 (presynaptic) receptors work cooperatively to promote neuroprotection against glutamate insult. Pharmacological blockade or genetic ablation of either receptor abolishes both CB1- and mGluR5-mediated neuroprotection. The neuroprotective mechanism involves MEK/ERK1/2 and PI3K/AKT signaling pathways, rather than reduced glutamate release or diminished intracellular Ca2+. Primary corticostriatal neuron cultures, pharmacological receptor blockade, genetic ablation, cell death assays, kinase inhibitors, signaling assays (ERK1/2, AKT phosphorylation) Molecular brain Medium 27543109
2017 mGluR5 agonist CHPG treatment increases RANTES production and amplifies irradiation-induced NF-κB activation in T lymphocytes, while mGluR5 inhibition with MPEP decreases RANTES after irradiation. mGluR5 receptors cluster following irradiation in T cells. T lymphocyte cell line (Jurkat E6.1), mGluR5 agonist/antagonist treatment, ELISA (RANTES), NF-κB/GFP reporter assay, immunofluorescence (receptor clustering) Translational psychiatry Medium 29849049
2017 Peripheral mGluR5 signaling sensitizes TRPV1 and TRPA1 via PKCε phosphorylation to produce thermal and mechanical hypersensitivity. Continuous facial skin injection of mGluR5 agonist (CHPG) or glutamate decreased pain thresholds, which were reversed by mGluR5 antagonist MTEP, TRPA1 antagonist, TRPV1 antagonist, or PKCε translocation inhibitor applied peripherally. PKCε phosphorylation in trigeminal ganglion was enhanced by glutamate treatment. In vivo pain behavioral assays, intraplantar pharmacological injections, Western blot (PKCε phosphorylation), immunohistochemistry (co-expression of mGluR5, TRPV1, TRPA1, PKCε) Pain Medium 28621704
2017 Melatonin/MT2 receptor signaling reduces pain by impeding Tet1-dependent demethylation of the mGluR5 promoter in spinal dorsal horn neurons. Spinal Tet1 gene transfer induces Tet1-mGluR5 promoter coupling, demethylation, and mGluR5 upregulation. Melatonin reverses Tet1-dependent mGluR5 promoter demethylation and associated mGluR5 expression and pain hypersensitivity via MT2 receptor. Intrathecal vector-mediated gene transfer, chromatin immunoprecipitation (Tet1-mGluR5 promoter), bisulfite sequencing (promoter methylation), intrathecal drug injection, behavioral pain testing, Western blot Journal of pineal research Medium 28718992
2018 Patients' IgG antibodies against mGluR5 (primarily IgG1, ±IgG2/IgG3) cause a significant and specific decrease of cell-surface synaptic and extrasynaptic mGluR5 without altering PSD-95 levels, demonstrating pathogenic effects of anti-mGluR5 antibodies in encephalitis. Cell-based assays (antibody application to rat hippocampal neurons), immunohistochemistry (brain), IgG subclass determination, quantitative receptor cluster analysis Neurology Medium 29703767
2018 mGluR5 hypofunction in schizophrenia postmortem DLPFC is characterized by decreased Gq/11 coupling, reduced mGluR5 association with PI3K and Homer, increased serine and tyrosine phosphorylation of mGluR5 (causing desensitization), and altered protein-protein interactions with RGS4, Norbin, Preso1, and Tamalin. Reduced mGluR5-GluN physical association provides a mechanistic basis for impaired reciprocal mGluR5-NMDA receptor facilitation in schizophrenia. Co-immunoprecipitation (mGluR5-Gq/11, mGluR5-PI3K, mGluR5-Homer, mGluR5-GluN, mGluR5-RGS4, mGluR5-Norbin, mGluR5-Preso1, mGluR5-Tamalin), phosphorylation assays, agonist-induced signaling assays in postmortem tissue Molecular psychiatry Medium 30214040
2019 Homer1a induction enhances mGluR5 signaling, resulting in increased mTOR pathway phosphorylation and upregulation of synaptic AMPA receptor expression. The antidepressant action of sleep deprivation and Homer1a induction requires mGluR5 activation specifically in excitatory CaMK2a neurons and depends on enhanced AMPA receptor activity, translation, and trafficking. Cell-permeable TAT-Homer1a peptide injection, conditional knockout (mGluR5 in CaMK2a+ excitatory neurons), electrophysiology, Western blot (mTOR phosphorylation), AMPA receptor surface expression assays, behavioral antidepressant assays Neuron High 31420117
2020 D1 dopamine receptor and mGluR5 form heteromeric receptor complexes on cell surfaces that couple to Gq proteins and produce synergistic PLC signaling and intracellular calcium release in response to either glutamate or dopamine. In dopamine-denervated striatum (Parkinson's disease model), D1-mGluR5 nanocomplexes are upregulated, leading to excessive ERK activation and dyskinesia. Co-immunoprecipitation, proximity ligation assay (nanoscale interaction), BRET/FRET (heteromer confirmation), calcium signaling assays, PLC assay, ERK phosphorylation assay in rodent PD models, behavioral dyskinesia testing The Journal of clinical investigation High 32039920
2020 FMRP deficiency in astroglia cell-autonomously upregulates miR-128-3p, which suppresses developmental mGluR5 expression in astrocytes. Selective in vivo inhibition of miR-128-3p in FMRP-deficient astroglia rescues decreased astroglial mGluR5 function. This FMRP→miR-128-3p→mGluR5 pathway is selective to astroglia and operates at the posttranscriptional level. Astrocyte-selective FMRP conditional knockout in vivo, miR-128-3p inhibition in vivo, mGluR5 functional assays, transcriptome and proteome profiling, Western blot Proceedings of the National Academy of Sciences of the United States of America High 32958647
2022 Astrocytic mGluR5, which transiently reemerges in adult somatosensory cortex astrocytes after nerve injury, drives Ca2+ signals and upregulates synaptogenic molecules (Thrombospondin-1, Glypican-4, Hevin), causing excess excitatory synaptogenesis and persistent mechanical allodynia. Astrocyte-specific deletion of mGluR5 abolishes all these events, establishing a causal role for astrocytic mGluR5 in pain-associated synaptic plasticity. Astrocyte-specific conditional knockout of mGluR5, Ca2+ imaging, immunohistochemistry (synaptogenic molecules), synaptic density quantification, behavioral pain testing (mechanical allodynia) The Journal of experimental medicine High 35319723
2022 Treatment with the mGluR5 silent allosteric modulator (SAM) BMS-984923 prevents Aβ oligomer-induced aberrant synaptic mGluR5 signaling while preserving physiological glutamate responses, restoring synaptic density in Alzheimer's disease mouse models. SAM treatment prevents synaptic localization of complement component C1Q and synaptic engulfment, and normalizes neuronal gene expression patterns. Oral SAM drug treatment in aged AD mouse models (APPswe/PS1ΔE9, App/hMapt knock-in), [18F]FPEB PET for brain mGluR5 occupancy, [18F]SynVesT-1 PET for synaptic density (SV2A), single-nuclei transcriptomics, C1Q immunohistochemistry, synaptic engulfment assay, behavioral testing Science translational medicine High 35648810
2023 mGluR5 is dynamically organized in perisynaptic nanodomains positioned close to but excluded from the synapse. The C-terminal domain of mGluR5 critically controls perisynaptic confinement and prevents synaptic entry. Forced recruitment of mGluR5 to the synapse (via inducible interaction system) acutely increases synaptic calcium responses, demonstrating that perisynaptic localization shapes synaptic function. Live-cell super-resolution imaging (single-molecule localization microscopy), inducible chemogenetic interaction system to overcome synaptic exclusion, synaptic calcium imaging, C-terminal domain mutagenesis/truncation Nature communications High 36646691
2024 The dimeric class C GPCR mGlu5 activates through an asymmetric, stepwise millisecond allosteric mechanism. Agonist binding induces dimeric ectodomain compaction amplified by cysteine-rich domain association, which loosely brings the 7TM domains into proximity establishing an asymmetric TM6-TM6 interface. Positive allosteric modulators stabilize the active inter-domain 7TM interface and an open ICL2 conformation, creating a pseudo-cavity (ICL2, ICL3, TM3, C-terminus) that facilitates G protein coordination. Markov state models (atomistic MD simulations), transition pathway generation, experimental signaling assays (validating simulation predictions) Nature communications Medium 39209876

Source papers

Stage 0 corpus · 100 papers · ranked by NIH iCite citations
Year Title Journal Citations PMID
1995 Distribution of metabotropic glutamate receptor mGluR5 immunoreactivity in rat brain. The Journal of comparative neurology 598 7636025
2001 Chemical induction of mGluR5- and protein synthesis--dependent long-term depression in hippocampal area CA1. Journal of neurophysiology 323 11431513
2007 FMRP mediates mGluR5-dependent translation of amyloid precursor protein. PLoS biology 243 17298186
2008 Role for metabotropic glutamate receptor 5 (mGluR5) in the pathogenesis of fragile X syndrome. The Journal of physiology 217 18202092
2001 mGlu5 receptors and nociceptive function II. mGlu5 receptors functionally expressed on peripheral sensory neurones mediate inflammatory hyperalgesia. Neuropharmacology 190 11077066
2009 mGluR5 positive allosteric modulators facilitate both hippocampal LTP and LTD and enhance spatial learning. Neuropsychopharmacology : official publication of the American College of Neuropsychopharmacology 187 19295507
1995 Differential expression of mGluR5 metabotropic glutamate receptor mRNA by rat striatal neurons. The Journal of comparative neurology 167 7782501
2001 Differential subcellular localization of mGluR1a and mGluR5 in the rat and monkey Substantia nigra. The Journal of neuroscience : the official journal of the Society for Neuroscience 146 11245668
2012 Delayed mGluR5 activation limits neuroinflammation and neurodegeneration after traumatic brain injury. Journal of neuroinflammation 143 22373400
2018 Encephalitis with mGluR5 antibodies: Symptoms and antibody effects. Neurology 140 29703767
2011 Autism, Alzheimer disease, and fragile X: APP, FMRP, and mGluR5 are molecular links. Neurology 120 21482951
2009 Intracellular metabotropic glutamate receptor 5 (mGluR5) activates signaling cascades distinct from cell surface counterparts. The Journal of biological chemistry 118 19840937
1995 Metabotropic glutamate receptor mGluR5 subcellular distribution and developmental expression in hypothalamus. The Journal of comparative neurology 113 8576426
2003 Metabotropic mGlu5 receptors regulate adenosine A2A receptor signaling. Proceedings of the National Academy of Sciences of the United States of America 111 12538871
2015 Biased mGlu5-Positive Allosteric Modulators Provide In Vivo Efficacy without Potentiating mGlu5 Modulation of NMDAR Currents. Neuron 105 25937172
2008 Metabotropic glutamate receptor 5 (mGluR5) regulation of ethanol sedation, dependence and consumption: relationship to acamprosate actions. The international journal of neuropsychopharmacology 99 18377703
2012 mGlu2/3 and mGlu5 receptors: potential targets for novel antidepressants. Neuropharmacology 98 22640631
2007 mGluR5 metabotropic glutamate receptors and dyskinesias in MPTP monkeys. Neurobiology of aging 98 17353071
1997 Metabotropic glutamate receptor mGluR5 in astrocytes: pharmacological properties and agonist regulation. Journal of neurochemistry 93 9202306
2003 Distribution of mGluR1alpha and mGluR5 immunolabeling in primate prefrontal cortex. The Journal of comparative neurology 92 14624486
2003 The metabotropic glutamate receptor mGluR5 is endocytosed by a clathrin-independent pathway. The Journal of biological chemistry 90 12529370
2003 Differential roles of mGluR1 and mGluR5 in brief and prolonged nociceptive processing in central amygdala neurons. Journal of neurophysiology 90 13679408
2017 Functional partnership between mGlu3 and mGlu5 metabotropic glutamate receptors in the central nervous system. Neuropharmacology 89 29079293
2014 Intracellular mGluR5 can mediate synaptic plasticity in the hippocampus. The Journal of neuroscience : the official journal of the Society for Neuroscience 86 24672004
2015 Astrocytic mGluR5 and the tripartite synapse. Neuroscience 82 25847307
2014 Fragile X syndrome: a preclinical review on metabotropic glutamate receptor 5 (mGluR5) antagonists and drug development. Psychopharmacology 78 24232444
2022 Reversal of synapse loss in Alzheimer mouse models by targeting mGluR5 to prevent synaptic tagging by C1Q. Science translational medicine 77 35648810
2016 Intracellular mGluR5 plays a critical role in neuropathic pain. Nature communications 76 26837579
2012 Role of mGluR5 neurotransmission in reinstated cocaine-seeking. Addiction biology 76 22340009
2011 Expression of the metabotropic glutamate receptor 5 (mGluR5) induces melanoma in transgenic mice. Proceedings of the National Academy of Sciences of the United States of America 75 21896768
2015 Therapeutic potential of mGluR5 targeting in Alzheimer's disease. Frontiers in neuroscience 74 26106290
2014 Changes in mGlu5 receptor-dependent synaptic plasticity and coupling to homer proteins in the hippocampus of Ube3A hemizygous mice modeling angelman syndrome. The Journal of neuroscience : the official journal of the Society for Neuroscience 72 24672001
2017 Synaptotoxic Signaling by Amyloid Beta Oligomers in Alzheimer's Disease Through Prion Protein and mGluR5. Advances in pharmacology (San Diego, Calif.) 67 29413525
2019 Enhanced mGlu5 Signaling in Excitatory Neurons Promotes Rapid Antidepressant Effects via AMPA Receptor Activation. Neuron 66 31420117
2013 The role of ventral and dorsal striatum mGluR5 in relapse to cocaine-seeking and extinction learning. Addiction biology 66 23710649
2015 Alteration by p11 of mGluR5 localization regulates depression-like behaviors. Molecular psychiatry 65 26370144
2004 mGlu5 receptor antagonists: a novel class of anxiolytics? Drug news & perspectives 65 15334174
2015 Homer1/mGluR5 activity moderates vulnerability to chronic social stress. Neuropsychopharmacology : official publication of the American College of Neuropsychopharmacology 61 25409593
2008 mGluR5 antagonists: discovery, characterization and drug development. Current opinion in drug discovery & development 59 18729017
2019 Modulation of mTOR and CREB pathways following mGluR5 blockade contribute to improved Huntington's pathology in zQ175 mice. Molecular brain 54 30961637
2013 mGlu5 negative allosteric modulators: a patent review (2010-2012). Expert opinion on therapeutic patents 54 23339457
2022 Transient astrocytic mGluR5 expression drives synaptic plasticity and subsequent chronic pain in mice. The Journal of experimental medicine 52 35319723
2007 Cellular localization of mGluR3 and mGluR5 mRNAs in normal and injured rat brain. Brain research 52 17428452
2020 PET imaging of mGluR5 in Alzheimer's disease. Alzheimer's research & therapy 51 31954399
2016 Regulation of Amyloid β Oligomer Binding to Neurons and Neurotoxicity by the Prion Protein-mGluR5 Complex. The Journal of biological chemistry 51 27563063
2018 Conditional Knock-out of mGluR5 from Astrocytes during Epilepsy Development Impairs High-Frequency Glutamate Uptake. The Journal of neuroscience : the official journal of the Society for Neuroscience 50 30504280
2006 The PDZ scaffold NHERF-2 interacts with mGluR5 and regulates receptor activity. The Journal of biological chemistry 50 16891310
2016 Direct current stimulation induces mGluR5-dependent neocortical plasticity. Annals of neurology 49 27315032
2020 D1-mGlu5 heteromers mediate noncanonical dopamine signaling in Parkinson's disease. The Journal of clinical investigation 46 32039920
2014 Location-dependent signaling of the group 1 metabotropic glutamate receptor mGlu5. Molecular pharmacology 45 25326002
2008 Presynaptic mGlu1 and mGlu5 autoreceptors facilitate glutamate exocytosis from mouse cortical nerve endings. Neuropharmacology 44 18625255
2010 Functional interaction of mGlu5 and NMDA receptors in aversive learning in rats. Neurobiology of learning and memory 43 21093598
2017 Sensitization of TRPV1 and TRPA1 via peripheral mGluR5 signaling contributes to thermal and mechanical hypersensitivity. Pain 42 28621704
2017 Melatonin impedes Tet1-dependent mGluR5 promoter demethylation to relieve pain. Journal of pineal research 42 28718992
2010 Operant sensation seeking requires metabotropic glutamate receptor 5 (mGluR5). PloS one 42 21152045
2018 mGluR5 hypofunction is integral to glutamatergic dysregulation in schizophrenia. Molecular psychiatry 41 30214040
2016 Functional role of striatal A2A, D2, and mGlu5 receptor interactions in regulating striatopallidal GABA neuronal transmission. Journal of neurochemistry 41 27127992
2004 Interactions between NMDA receptors and mGlu5 receptors expressed in HEK293 cells. British journal of pharmacology 41 15210575
2019 In vivo evidence for dysregulation of mGluR5 as a biomarker of suicidal ideation. Proceedings of the National Academy of Sciences of the United States of America 40 31085640
2015 Shifting towards a model of mGluR5 dysregulation in schizophrenia: Consequences for future schizophrenia treatment. Neuropharmacology 40 26349010
2015 Convergent evidence for mGluR5 in synaptic and neuroinflammatory pathways implicated in ASD. Neuroscience and biobehavioral reviews 38 25704074
2015 Alterations of mGluR5 and its endogenous regulators Norbin, Tamalin and Preso1 in schizophrenia: towards a model of mGluR5 dysregulation. Acta neuropathologica 37 25778620
2009 The promiscuous mGlu5 receptor--a range of partners for therapeutic possibilities? Trends in pharmacological sciences 36 19892412
2012 PKC phosphorylation regulates mGluR5 trafficking by enhancing binding of Siah-1A. The Journal of neuroscience : the official journal of the Society for Neuroscience 34 23152621
2013 mGluR5 ablation in cortical glutamatergic neurons increases novelty-induced locomotion. PloS one 33 23940572
2012 Constitutive internalization and recycling of metabotropic glutamate receptor 5 (mGluR5). Biochemical and biophysical research communications 33 22995293
2023 mGluR5 is transiently confined in perisynaptic nanodomains to shape synaptic function. Nature communications 32 36646691
2021 mGluR5 Negative Modulators for Fragile X: Treatment Resistance and Persistence. Frontiers in psychiatry 32 34658956
2019 Alterations in sleep, sleep spindle, and EEG power in mGluR5 knockout mice. Journal of neurophysiology 32 31747354
2001 Gene targeting reveals a role for the glutamate receptors mGluR5 and GluR2 in learning and memory. Physiology & behavior 32 11566212
2017 mGlu5 negative allosteric modulators: a patent review (2013 - 2016). Expert opinion on therapeutic patents 31 28067079
2004 Allosteric modulators of metabotropic glutamate receptors: lessons learnt from mGlu1, mGlu2 and mGlu5 potentiators and antagonists. Biochemical Society transactions 31 15494040
2018 Effects of common GRM5 genetic variants on cognition, hippocampal volume and mGluR5 protein levels in schizophrenia. Brain imaging and behavior 30 28405888
2012 Metabotropic glutamate receptor 5 (mGluR5) regulates bladder nociception. Molecular pain 29 22449017
2024 Delineating the stepwise millisecond allosteric activation mechanism of the class C GPCR dimer mGlu5. Nature communications 28 39209876
2015 Homer 1a and mGluR5 phosphorylation in reward-sensitive metaplasticity: A hypothesis of neuronal selection and bidirectional synaptic plasticity. Brain research 28 26187757
2011 RGS4 overexpression in the rat dorsal striatum modulates mGluR5- and amphetamine-mediated behavior and signaling. Psychopharmacology 28 22193724
2019 Age dependency of mGluR5 availability in 5xFAD mice measured by PET. Neurobiology of aging 27 31570178
2010 Interactive effects of mGlu5 and 5-HT2A receptors on locomotor activity in mice. Psychopharmacology 27 21153406
2009 Expression of metabotropic glutamate receptor mGluR5 in human dental pulp. Journal of endodontics 27 19410084
2017 Osteosarcoma cell proliferation and survival requires mGluR5 receptor activity and is blocked by Riluzole. PloS one 26 28231291
2016 Emotional Impairment and Persistent Upregulation of mGlu5 Receptor following Morphine Abstinence: Implications of an mGlu5-MOPr Interaction. The international journal of neuropsychopharmacology 26 26861145
2015 mGlu₅-GABAB interplay in animal models of positive, negative and cognitive symptoms of schizophrenia. Neurochemistry international 26 25863284
2012 Pilocarpine-induced status epilepticus increases Homer1a and changes mGluR5 expression. Epilepsy research 26 22591751
2010 Radioligands for the PET imaging of metabotropic glutamate receptor subtype 5 (mGluR5). Current topics in medicinal chemistry 26 20583985
2018 mGluR5 mediates post-radiotherapy fatigue development in cancer patients. Translational psychiatry 25 29849049
2013 Cellular distribution of AMPA receptor subunits and mGlu5 following acute and repeated administration of morphine or methamphetamine. Journal of neurochemistry 25 23711322
2005 Blockade of the mGlu5 receptor decreases basal and stress-induced cortical norepinephrine in rodents. Psychopharmacology 25 15717212
2019 Ultrastructural localization of cannabinoid CB1 and mGluR5 receptors in the prefrontal cortex and amygdala. The Journal of comparative neurology 24 31008528
2019 Pathophysiological clues to therapeutic applications of glutamate mGlu5 receptor antagonists in levodopa-induced dyskinesia. European journal of pharmacology 24 31063776
2019 Measuring the effects of ketamine on mGluR5 using [18F]FPEB and PET. Journal of cerebral blood flow and metabolism : official journal of the International Society of Cerebral Blood Flow and Metabolism 24 31744389
2014 The mGlu5 receptor regulates extinction of cocaine-driven behaviours. Drug and alcohol dependence 24 24576814
2014 Nanoscopic spine localization of Norbin, an mGluR5 accessory protein. BMC neuroscience 23 24670218
2005 Grm5 expression is not required for the oncogenic role of Grm1 in melanocytes. Neuropharmacology 23 16040064
2021 mGlu5 function in the nucleus accumbens core during the incubation of methamphetamine craving. Neuropharmacology 22 33444640
2013 Is the mGlu5 receptor a possible target for new antidepressant drugs? Pharmacological reports : PR 22 24552998
2024 Metabotropic glutamate receptor 5 (mGluR5) is associated with neurodegeneration and amyloid deposition in Alzheimer's disease: A [18F]PSS232 PET/MRI study. Alzheimer's research & therapy 21 38217040
2021 Genetic disruption of Grm5 causes complex alterations in motor activity, anxiety and social behaviors. Behavioural brain research 21 34029630
2020 Astroglial FMRP deficiency cell-autonomously up-regulates miR-128 and disrupts developmental astroglial mGluR5 signaling. Proceedings of the National Academy of Sciences of the United States of America 21 32958647
2016 Orchestrated activation of mGluR5 and CB1 promotes neuroprotection. Molecular brain 21 27543109

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