Genomes and Genes
Gene Symbol: Grm2
Description: glutamate receptor, metabotropic 2
Alias: 4930441L02Rik, Gprc1b, mGluR2, mGluR7, metabotropic glutamate receptor 2, G protein-coupled receptor, family C, group 1, member B
- Linden A, Shannon H, Baez M, Yu J, Koester A, Schoepp D. Anxiolytic-like activity of the mGLU2/3 receptor agonist LY354740 in the elevated plus maze test is disrupted in metabotropic glutamate receptor 2 and 3 knock-out mice. Psychopharmacology (Berl). 2005;179:284-91 pubmed
- Higgins G, Ballard T, Kew J, Richards J, Kemp J, Adam G, et al. Pharmacological manipulation of mGlu2 receptors influences cognitive performance in the rodent. Neuropharmacology. 2004;46:907-17 pubmed..Conversely, mGlu2 receptor antagonists may improve certain aspects of cognition and thus represent a novel approach for the symptomatic treatment of AD. ..
- Daumas S, Ceccom J, Halley H, Frances B, Lassalle J. Activation of metabotropic glutamate receptor type 2/3 supports the involvement of the hippocampal mossy fiber pathway on contextual fear memory consolidation. Learn Mem. 2009;16:504-7 pubmed publisher..Our results emphasize the major role played by the DG and CA3 areas in the early phases of contextual memory processing, particularly during the acquisition and early consolidation phases of CFC. ..
- Kew J, Pflimlin M, Kemp J, Mutel V. Differential regulation of synaptic transmission by mGlu2 and mGlu3 at the perforant path inputs to the dentate gyrus and CA1 revealed in mGlu2 -/- mice. Neuropharmacology. 2002;43:215-21 pubmed
- Kawasaki T, Ago Y, Yano K, Araki R, Washida Y, Onoe H, et al. Increased binding of cortical and hippocampal group II metabotropic glutamate receptors in isolation-reared mice. Neuropharmacology. 2011;60:397-404 pubmed publisher..In view of the recent studies that the group II metabotropic glutamate receptor (mGluR2/3) is involved in neuropsychiatric disorders, the present study examined the effect of isolation rearing on the ..
- Nasca C, Xenos D, Barone Y, Caruso A, Scaccianoce S, Matrisciano F, et al. L-acetylcarnitine causes rapid antidepressant effects through the epigenetic induction of mGlu2 receptors. Proc Natl Acad Sci U S A. 2013;110:4804-9 pubmed publisher..In both models, LAC increased levels of acetylated H3K27 bound to the Grm2 promoter and also increased acetylation of NF-?B-p65 subunit, thereby enhancing the transcription of Grm2 gene ..
- Koren D, Grove J, Wei W. Cross-compartmental Modulation of Dendritic Signals for Retinal Direction Selectivity. Neuron. 2017;95:914-927.e4 pubmed publisher..However, the mechanism that regulates this propagation is poorly understood. Here, we find that metabotropic glutamate receptor 2 (mGluR2) signaling, which acts on voltage-gated calcium channels in SACs, selectively restricts ..
- Borges Merjane C, Trussell L. ON and OFF unipolar brush cells transform multisensory inputs to the auditory system. Neuron. 2015;85:1029-42 pubmed publisher..ByÂ analogy to the retina, we propose that UBCs comprise ON and OFF cells with respect to their response to glutamatergic input and may therefore provide distinct parallel processing of multisensory input to their targets. ..
- Dedeurwaerdere S, Wintmolders C, Straetemans R, Pemberton D, Langlois X. Memantine-induced brain activation as a model for the rapid screening of potential novel antipsychotic compounds: exemplified by activity of an mGlu2/3 receptor agonist. Psychopharmacology (Berl). 2011;214:505-14 pubmed publisher..This novel pre-clinical imaging methodology displays potential for the screening of compounds targeting the NMDA receptor hypofunction hypothesis of schizophrenia and should assist in developing compounds from the bench to clinic. ..
- Thomsen C, Klitgaard H, Sheardown M, Jackson H, Eskesen K, Jacobsen P, et al. (S)-4-carboxy-3-hydroxyphenylglycine, an antagonist of metabotropic glutamate receptor (mGluR) 1a and an agonist of mGluR2, protects against audiogenic seizures in DBA/2 mice. J Neurochem. 1994;62:2492-5 pubmed..S)-4C3HPG was, however, an agonist at mGluR2 with an EC50 of 21 +/- 4 microM for inhibition of forskolin-stimulated cyclic AMP formation in BHK cells ..
- Cannella N, Halbout B, Uhrig S, Evrard L, Corsi M, Corti C, et al. The mGluR2/3 agonist LY379268 induced anti-reinstatement effects in rats exhibiting addiction-like behavior. Neuropsychopharmacology. 2013;38:2048-56 pubmed publisher..In particular, it has been shown that metabotropic glutamate receptor 2/3 (mGluR2/3)-mediated long-term depression is suppressed in the prelimbic cortex in addict-like rats...
- Richards G, Messer J, Faull R, Stadler H, Wichmann J, Huguenin P, et al. Altered distribution of mGlu2 receptors in ?-amyloid-affected brain regions of Alzheimer cases and aged PS2APP mice. Brain Res. 2010;1363:180-90 pubmed publisher..These findings have implications for the development of selective ligands for symptomatic therapy in AD and for its diagnosis. ..
- Chiechio S, Copani A, De Petris L, Morales M, Nicoletti F, Gereau R. Transcriptional regulation of metabotropic glutamate receptor 2/3 expression by the NF-kappaB pathway in primary dorsal root ganglia neurons: a possible mechanism for the analgesic effect of L-acetylcarnitine. Mol Pain. 2006;2:20 pubmed..pain in humans, has been shown to induce analgesia in rodents by up-regulating the expression of metabotropic glutamate receptor 2 (mGlu2) in dorsal root ganglia (DRG)...
- Ahnaou A, Ver Donck L, Drinkenburg W. Blockade of the metabotropic glutamate (mGluR2) modulates arousal through vigilance states transitions: evidence from sleep-wake EEG in rodents. Behav Brain Res. 2014;270:56-67 pubmed publisherAccumulating data continue to support the therapeutic potential of glutamate metabotropic (mGluR2) receptors for treatment of psychiatric disorders such as depression, anxiety and schizophrenia...
- Moreno J, Muguruza C, Umali A, Mortillo S, Holloway T, Pilar Cuéllar F, et al. Identification of three residues essential for 5-hydroxytryptamine 2A-metabotropic glutamate 2 (5-HT2A·mGlu2) receptor heteromerization and its psychoactive behavioral function. J Biol Chem. 2012;287:44301-19 pubmed publisher..Together, these findings provide structural evidence for the unique behavioral function of a GPCR heteromer. ..
- Battaglia G, Riozzi B, Bucci D, Di Menna L, Molinaro G, Pallottino S, et al. Activation of mGlu3 metabotropic glutamate receptors enhances GDNF and GLT-1 formation in the spinal cord and rescues motor neurons in the SOD-1 mouse model of amyotrophic lateral sclerosis. Neurobiol Dis. 2015;74:126-36 pubmed publisher..LY379268 had no significant effect on the mortality rate of SODG93A. These findings encourage the development of selective mGlu3 receptor agonists/enhancers as neuroprotective agents in ALS. ..
- Fribourg M, Moreno J, Holloway T, Provasi D, Baki L, Mahajan R, et al. Decoding the signaling of a GPCR heteromeric complex reveals a unifying mechanism of action of antipsychotic drugs. Cell. 2011;147:1011-23 pubmed publisher..now show that a heteromeric complex between the 2AR and the G(i)-linked GPCR, metabotropic glutamate 2 receptor (mGluR2), integrates ligand input, modulating signaling output and behavioral changes...
- Nicholls R, Zhang X, Bailey C, Conklin B, Kandel E, Stanton P. mGluR2 acts through inhibitory Galpha subunits to regulate transmission and long-term plasticity at hippocampal mossy fiber-CA3 synapses. Proc Natl Acad Sci U S A. 2006;103:6380-5 pubmed..b>mGluR2 participates in at least three types of mossy fiber synaptic plasticity, (i) transient suppression of synaptic ..
- Marino S, Krimpenfort P, Leung C, van der Korput H, Trapman J, Camenisch I, et al. PTEN is essential for cell migration but not for fate determination and tumourigenesis in the cerebellum. Development. 2002;129:3513-22 pubmed..However, PTEN is not required for cell differentiation and lack of PTEN is not sufficient to induce neoplastic transformation of neuronal or glial cells ..
- Yin S, Noetzel M, Johnson K, Zamorano R, Jalan Sakrikar N, Gregory K, et al. Selective actions of novel allosteric modulators reveal functional heteromers of metabotropic glutamate receptors in the CNS. J Neurosci. 2014;34:79-94 pubmed publisher..These data greatly extend our current understanding of mGlu receptor interaction and function and provide compelling evidence that mGlu receptors can function as heteromers in intact brain circuits. ..
- Aguado C, Fernandez Alacid L, Cabañero M, Yanagawa Y, Schilling K, Watanabe M, et al. Differential maturation of GIRK2-expressing neurons in the mouse cerebellum. J Chem Neuroanat. 2013;47:79-89 pubmed publisher..characterization on the expression of GIRK2 in different subpopulations of Golgi cells, using metabotropic glutamate receptor 2 (mGlu(2)) and neurogranin as markers, in GlyT2-GFP and GAD67-GFP mice, and showed that GIRK2 is ..
- 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..We examined the fear response of freezing after electric shock in wild-type and mGluR7(-/-) knockout littermates. Wild-type mice displayed freezing immediately after and 1 d after footshock...
- Negrete Diaz J, Sihra T, Delgado Garcia J, Rodriguez Moreno A. Kainate receptor-mediated presynaptic inhibition converges with presynaptic inhibition mediated by Group II mGluRs and long-term depression at the hippocampal mossy fiber-CA3 synapse. J Neural Transm (Vienna). 2007;114:1425-31 pubmed..The mutual occlusion of depression mediated by presynaptic KARs, Group II mGluR and LFS-induced LTD suggests their mechanistic convergence at the MF-CA3 synapse and thus invokes KARs in synaptic plasticity manifest in LTD. ..
- Nishizaki Y, Takagi T, Matsui F, Higashi Y. SIP1 expression patterns in brain investigated by generating a SIP1-EGFP reporter knock-in mouse. Genesis. 2014;52:56-67 pubmed publisher..These findings may help to clarify the unknown roles of SIP1 in these cells and the pathoetiology of Mowat-Wilson syndrome. ..
- Moreno J, Kurita M, Holloway T, Lopez J, Cadagan R, Martinez Sobrido L, et al. Maternal influenza viral infection causes schizophrenia-like alterations of 5-HT?A and mGlu? receptors in the adult offspring. J Neurosci. 2011;31:1863-72 pubmed publisher..Identifying a biochemical alteration that parallels the behavioral changes observed in a mouse model of prenatal viral infection may facilitate targeting therapies for treatment and prevention of schizophrenia. ..
- Moreno J, Miranda Azpiazu P, GarcÃa Bea A, Younkin J, Cui M, Kozlenkov A, et al. Allosteric signaling through an mGlu2 and 5-HT2A heteromeric receptor complex and its potential contribution to schizophrenia. Sci Signal. 2016;9:ra5 pubmed publisher..These findings offer structural insights into this important target in molecular psychiatry. ..
- Walker A, Wenthur C, Xiang Z, Rook J, Emmitte K, Niswender C, et al. Metabotropic glutamate receptor 3 activation is required for long-term depression in medial prefrontal cortex and fear extinction. Proc Natl Acad Sci U S A. 2015;112:1196-201 pubmed publisher..The results of these studies implicate mGlu3 as a major regulator of PFC function and cognition. Additionally, potentiators of mGlu3 may be useful in alleviating prefrontal impairments associated with several CNS disorders. ..
- Perroy J, Gutierrez G, Coulon V, Bockaert J, Pin J, Fagni L. The C terminus of the metabotropic glutamate receptor subtypes 2 and 7 specifies the receptor signaling pathways. J Biol Chem. 2001;276:45800-5 pubmed..These results show that the C terminus of mGlu2 and mGlu7 receptors is a key structural determinant that allows these receptors to select a specific signaling pathway in neurons. ..
- Kupferschmidt D, Lovinger D. Inhibition of presynaptic calcium transients in cortical inputs to the dorsolateral striatum by metabotropic GABA(B) and mGlu2/3 receptors. J Physiol. 2015;593:2295-310 pubmed publisher..These findings reveal presynaptic mechanisms of inhibitory modulation of corticostriatal function that probably contribute to the selection and shaping of behavioural repertoires. ..
- 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. ..
- Johnson K, Mateo Y, Lovinger D. Metabotropic glutamate receptor 2 inhibits thalamically-driven glutamate and dopamine release in the dorsal striatum. Neuropharmacology. 2017;117:114-123 pubmed publisher..recently-discovered pharmacological tools to dissect the effects of a prominent presynaptic GPCR, metabotropic glutamate receptor 2 (mGlu2), on corticostriatal vs. thalamostriatal transmission...
- Bergmann M, Fox P, Grabs D, Post A, Schilling K. Expression and subcellular distribution of glutamate receptor subunits 2/3 in the developing cerebellar cortex. J Neurosci Res. 1996;43:78-86 pubmed..The presence of membrane bond receptors prior to the formation of synapses also provides a rationale for the known transmitter-mediated modulation of Purkinje cell dendritogenesis. ..
- McOmish C, Demireva E, Gingrich J. Developmental expression of mGlu2 and mGlu3 in the mouse brain. Gene Expr Patterns. 2016;22:46-53 pubmed publisher..These studies provide a foundation for future research seeking to parse out the roles of mGlu2 from mGlu3, paving the way for better understanding of how these receptors regulate activity in the brain. ..
- Okamoto R, Itoh Y, Murata Y, Kobayashi D, Hosoi M, Mine K. Reduction of group II metabotropic glutamate receptors during development of benzodiazepine dependence. Pharmacology. 2013;91:145-52 pubmed publisher..The mRNA expression levels of mGluR2 and mGluR3 were lowered in the cerebral cortex of mice pretreated with diazepam or alprazolam...
- Lam Y, Sherman S. Activation of both Group I and Group II metabotropic glutamatergic receptors suppress retinogeniculate transmission. Neuroscience. 2013;242:78-84 pubmed publisher..We also found high-frequency stimulation of the layer 6 corticothalamic input produced a similar suppression of retinogeniculate EPSCs, suggesting layer 6 projection to LGN as a plausible source of activating these presynaptic mGluRs. ..
- Coate T, Raft S, Zhao X, Ryan A, Crenshaw E, Kelley M. Otic mesenchyme cells regulate spiral ganglion axon fasciculation through a Pou3f4/EphA4 signaling pathway. Neuron. 2012;73:49-63 pubmed publisher..These results indicate a model whereby Pou3f4 in the otic mesenchyme establishes an Eph/ephrin-mediated fasciculation signal that promotes inner radial bundle formation. ..
- Fukami S, Watanabe K, Iwata N, Haraoka J, Lu B, Gerard N, et al. Abeta-degrading endopeptidase, neprilysin, in mouse brain: synaptic and axonal localization inversely correlating with Abeta pathology. Neurosci Res. 2002;43:39-56 pubmed
- Linden A, Johnson B, Trokovic N, Korpi E, Schoepp D. Use of MGLUR2 and MGLUR3 knockout mice to explore in vivo receptor specificity of the MGLUR2/3 selective antagonist LY341495. Neuropharmacology. 2009;57:172-82 pubmed publisherLY341495 is a metabotropic glutamate receptor (mGluR) antagonist showing selectivity to mGluR2/3 but having measurable antagonist efficacy across all mGluR subtypes at 10-1000 fold higher concentrations...
- Zhou Z, Karlsson C, Liang T, Xiong W, Kimura M, Tapocik J, et al. Loss of metabotropic glutamate receptor 2 escalates alcohol consumption. Proc Natl Acad Sci U S A. 2013;110:16963-8 pubmed publisher..analysis, and functional validation, we identified that genetic variation of Grm2, which encodes metabotropic glutamate receptor 2 (mGluR2), alters alcohol preference in animal models...
- Ster J, Mateos J, Grewe B, Coiret G, Corti C, Corsi M, et al. Enhancement of CA3 hippocampal network activity by activation of group II metabotropic glutamate receptors. Proc Natl Acad Sci U S A. 2011;108:9993-7 pubmed publisher..Experiments with transgenic mice revealed a significant reduction of the inward current in mGluR3(-/-) but not in mGluR2(-/-) mice. The excitatory response was associated with periods of synchronized activity at theta frequency...
- Englund C, Kowalczyk T, Daza R, Dagan A, Lau C, Rose M, et al. Unipolar brush cells of the cerebellum are produced in the rhombic lip and migrate through developing white matter. J Neurosci. 2006;26:9184-95 pubmed..Our findings support a model of cerebellar neurogenesis, in which glutamatergic and GABAergic neurons are produced from separate progenitor pools located mainly in the rhombic lip and the cerebellar ventricular zone, respectively. ..
- Pritchett D, Jagannath A, Brown L, Tam S, Hasan S, Gatti S, et al. Deletion of Metabotropic Glutamate Receptors 2 and 3 (mGlu2 & mGlu3) in Mice Disrupts Sleep and Wheel-Running Activity, and Increases the Sensitivity of the Circadian System to Light. PLoS ONE. 2015;10:e0125523 pubmed publisher..system, and in particular, the group II metabotropic glutamate receptors mGlu2 and mGlu3 (encoded by the genes Grm2 and Grm3)...
- Moreno J, Holloway T, Albizu L, Sealfon S, Gonzalez Maeso J. Metabotropic glutamate mGlu2 receptor is necessary for the pharmacological and behavioral effects induced by hallucinogenic 5-HT2A receptor agonists. Neurosci Lett. 2011;493:76-9 pubmed publisher..b>Metabotropic glutamate receptor 2/3 (mGluR2/3) ligands show efficacy in modulating the responses induced by activation of 5-HT2ARs...
- Renger J, Hartman K, Tsuchimoto Y, Yokoi M, Nakanishi S, Hensch T. Experience-dependent plasticity without long-term depression by type 2 metabotropic glutamate receptors in developing visual cortex. Proc Natl Acad Sci U S A. 2002;99:1041-6 pubmed..Here, we establish a fundamental role for type 2 metabotropic glutamate receptors (mGluR2) in long-term depression (LTD) of synaptic transmission within primary visual cortex...
- Schmitz S, King C, Kortleven C, Huson V, Kroon T, Kevenaar J, et al. Presynaptic inhibition upon CB1 or mGlu2/3 receptor activation requires ERK/MAPK phosphorylation of Munc18-1. EMBO J. 2016;35:1236-50 pubmed publisherPresynaptic cannabinoid (CB1R) and metabotropic glutamate receptors (mGluR2/3) regulate synaptic strength by inhibiting secretion...
- Chavis P, Shinozaki H, Bockaert J, Fagni L. The metabotropic glutamate receptor types 2/3 inhibit L-type calcium channels via a pertussis toxin-sensitive G-protein in cultured cerebellar granule cells. J Neurosci. 1994;14:7067-76 pubmed..This effect was mimicked by (2S,1'S,2'S)-2-(carboxycyclopropyl)glycine (L-CCG-I), a selective agonist of mGluR2/R3 receptors, but not by quisqualate at a concentration that stimulated inositol phosphate (InsP) synthesis, ..
- Kurita M, Moreno J, Holloway T, Kozlenkov A, Mocci G, García Bea A, et al. Repressive epigenetic changes at the mGlu2 promoter in frontal cortex of 5-HT2A knockout mice. Mol Pharmacol. 2013;83:1166-75 pubmed publisher..Together, these observations suggest that 5-HT(2A) receptor-dependent signaling epigenetically affects mGlu2 transcription in mouse frontal cortex. ..
- De Filippis B, Lyon L, Taylor A, Lane T, Burnet P, Harrison P, et al. The role of group II metabotropic glutamate receptors in cognition and anxiety: comparative studies in GRM2(-/-), GRM3(-/-) and GRM2/3(-/-) knockout mice. Neuropharmacology. 2015;89:19-32 pubmed publisherGroup II metabotropic glutamate receptors (mGlu2 and mGlu3, encoded by GRM2 and GRM3) have been implicated in both cognitive and emotional processes, although their precise role remains to be established...
- Matrisciano F, Tueting P, Maccari S, Nicoletti F, Guidotti A. Pharmacological activation of group-II metabotropic glutamate receptors corrects a schizophrenia-like phenotype induced by prenatal stress in mice. Neuropsychopharmacology. 2012;37:929-38 pubmed publisher..Our data show for the first time that PRS induces a schizophrenia-like phenotype in mice, and suggest that epigenetic changes in mGlu2 and mGlu3 receptors lie at the core of the pathological programming induced by early-life stress. ..