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Gene Review

Grm4  -  glutamate receptor, metabotropic 4

Mus musculus

Synonyms: Gprc1d, Metabotropic glutamate receptor 4, Mglur4, mGluR4
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Disease relevance of Grm4

  • The finding that mGluR4 may selectively modulate striatopallidal transmission raises the interesting possibility that activation of mGluR4 could decrease the excessive inhibition of the GP that has been postulated to occur in Parkinson's disease [1].
  • In contrast, the mGluR4(-/-) mice were markedly resistant to absence seizures induced by low doses of GABA(A)R antagonists [2].

Psychiatry related information on Grm4

  • The mGluR4 mutant mice displayed normal spontaneous motor activity and were unimpaired on the bar cross test, indicating that disruption of the mGluR4 gene did not cause gross motor abnormalities, impairments of novelty-induced exploratory behaviors, or alterations in fine motor coordination [3].
  • Regulation of neurotransmission via group-III metabotropic glutamate receptors (mGluR4, -6, -7, and -8) has recently been implicated in the pathophysiology of affective disorders, such as major depression and anxiety [4].
  • These results show that mGluR4 may play a role in locomotor activity in general and also display specificity for mediation of the motor stimulant effect of ethanol [5].
  • No differences were observed between mGluR4(-/-) and mGluR4(+/+) mice in threshold to clonic or tonic seizures induced by higher doses of GABA(A)R antagonists, strychnine, or electroshock, indicating that seizure resistance in the mGluR4(-/-) mice was restricted solely to absence seizures [2].

High impact information on Grm4

  • Recent molecular biological results suggest that the metabotropic glutamate receptor mGluR4 may function in glutamate taste transduction [6].
  • We have also examined neurodegeneration induced by intrastriatal infusion of NMDA in wild-type or mGluR4-deficient mice [7].
  • Finally, microdialysis studies showed that intrastriatal infusion of NMDA increased extracellular glutamate levels to a greater extent in -/- than in +/+ mice, supporting the hypothesis that the mGluR4 subtype is necessary for the maintenance of the homeostasis of extracellular glutamate levels [7].
  • Conversely, intra-nRT administration of a mGluR4 agonist in mGluR4(+/+) mice exacerbated GABA(A)R-induced absence seizures [2].
  • There was no difference between mGluR4(-/-) and mGluR4(+/+) mice in threshold to absence seizures induced by either GHB or (-) baclofen [2].

Biological context of Grm4


Anatomical context of Grm4

  • In the hippocampus, mGluR4 labelling was prominent in the dentate molecular layer and CA1-3 strata lacunosum moleculare and oriens [8].
  • The antibodies reacted specifically with mGluR4 and not with other mGluRs in transfected COS 7 cells [8].
  • Somatodendritic profiles of some stratum oriens/alveus interneurones were richly decorated with mGluR4-labelled axon terminals making either type I or II synapses [8].
  • Interestingly, mGluR4 mRNA was found at a high level in cerebellar granule cells and at a lower level in cortical neurons and glial cells [12].
  • The moderate levels of binding observed with wild-type mice in the molecular layer of the hippocampal dentate gyrus and in the thalamus were absent in mGluR4 knock-out mice [9].

Associations of Grm4 with chemical compounds

  • Impaired cerebellar synaptic plasticity and motor performance in mice lacking the mGluR4 subtype of metabotropic glutamate receptor [3].
  • Pharmacological activation of mGluR7 by L-AP4 in both wild-type and mGluR4/8 double knockout mice selectively reduced fEPSPs in the MPP, but not LPP, and this level of inhibition was significantly reduced 3-9 days after PILO-induced SE [13].
  • The taste perception of monosodium glutamate (MSG) is termed 'umami'. Two putative taste receptors for glutamate have been identified, a truncated form of mGluR4 (taste-mGluR4) and the presumed heterodimer T1R1 + T1R3 [14].
  • Group III metabotropic glutamate receptors (mGluR4, 6, 7, 8) are negatively coupled to adenylate cyclase and, when activated presynaptically, decrease the release of glutamate and GABA [15].

Other interactions of Grm4

  • To provide a better understanding of the function of L-AP4 receptors, we have generated and studied knockout (KO) mice lacking the mGluR4 subtype of mGluR that displays high affinity for L-AP4 [3].
  • Similar experiments revealed that cerebellar granule cells expressed mGluR2-like and mGluR4-like receptors [12].
  • These data indicate that the presence of mGluR4 within nRT is critical to GABAergic modulation of thalamocortical synchronization in normal and pathological states, such as generalized absence epilepsy [2].
  • In these regions, mGluR8 is likely to be labeled by [3H]L-AP4 because mGluR8 is expressed in such brain regions and, like mGluR4, has high affinity for L-AP4 [9].

Analytical, diagnostic and therapeutic context of Grm4

  • The coexpression of mGluR4 and gb1a led to the expression of gb1a monomers on cell surface membranes as determined by immunoblot analysis and flow cytometry [16].


  1. Group III metabotropic glutamate receptor-mediated modulation of the striatopallidal synapse. Valenti, O., Marino, M.J., Wittmann, M., Lis, E., DiLella, A.G., Kinney, G.G., Conn, P.J. J. Neurosci. (2003) [Pubmed]
  2. Modulation of absence seizures by the GABA(A) receptor: a critical rolefor metabotropic glutamate receptor 4 (mGluR4). Snead, O.C., Banerjee, P.K., Burnham, M., Hampson, D. J. Neurosci. (2000) [Pubmed]
  3. Impaired cerebellar synaptic plasticity and motor performance in mice lacking the mGluR4 subtype of metabotropic glutamate receptor. Pekhletski, R., Gerlai, R., Overstreet, L.S., Huang, X.P., Agopyan, N., Slater, N.T., Abramow-Newerly, W., Roder, J.C., Hampson, D.R. J. Neurosci. (1996) [Pubmed]
  4. Metabotropic glutamate receptor subtype 7 ablation causes dysregulation of the HPA axis and increases hippocampal BDNF protein levels: implications for stress-related psychiatric disorders. Mitsukawa, K., Mombereau, C., Lötscher, E., Uzunov, D.P., van der Putten, H., Flor, P.J., Cryan, J.F. Neuropsychopharmacology (2006) [Pubmed]
  5. Mice lacking metabotropic glutamate receptor 4 do not show the motor stimulatory effect of ethanol. Blednov, Y.A., Walker, D., Osterndorf-Kahanek, E., Harris, R.A. Alcohol (2004) [Pubmed]
  6. Mechanisms of taste transduction. Kinnamon, S.C., Margolskee, R.F. Curr. Opin. Neurobiol. (1996) [Pubmed]
  7. Selective activation of mGlu4 metabotropic glutamate receptors is protective against excitotoxic neuronal death. Bruno, V., Battaglia, G., Ksiazek, I., van der Putten, H., Catania, M.V., Giuffrida, R., Lukic, S., Leonhardt, T., Inderbitzin, W., Gasparini, F., Kuhn, R., Hampson, D.R., Nicoletti, F., Flor, P.J. J. Neurosci. (2000) [Pubmed]
  8. Distribution and synaptic localisation of the metabotropic glutamate receptor 4 (mGluR4) in the rodent CNS. Corti, C., Aldegheri, L., Somogyi, P., Ferraguti, F. Neuroscience (2002) [Pubmed]
  9. Contribution of metabotropic glutamate receptor mGluR4 to L-2-[3H]amino-4-phosphonobutyrate binding in mouse brain. Thomsen, C., Hampson, D.R. J. Neurochem. (1999) [Pubmed]
  10. The actin-binding protein Filamin-A interacts with the metabotropic glutamate receptor type 7. Enz, R. FEBS Lett. (2002) [Pubmed]
  11. Localization of the human mGluR4 gene within an epilepsy susceptibility locus(1). Wong, C.G., Scherer, S.W., Snead, O.C., Hampson, D.R. Brain Res. Mol. Brain Res. (2001) [Pubmed]
  12. Pharmacological characterization of metabotropic glutamate receptors in several types of brain cells in primary cultures. Prézeau, L., Carrette, J., Helpap, B., Curry, K., Pin, J.P., Bockaert, J. Mol. Pharmacol. (1994) [Pubmed]
  13. Medial perforant path inhibition mediated by mGluR7 is reduced after status epilepticus. Bough, K.J., Mott, D.D., Dingledine, R.J. J. Neurophysiol. (2004) [Pubmed]
  14. Behavioral evidence for a role of alpha-gustducin in glutamate taste. Ruiz, C.J., Wray, K., Delay, E., Margolskee, R.F., Kinnamon, S.C. Chem. Senses (2003) [Pubmed]
  15. Convulsant and anticonvulsant actions of agonists and antagonists of group III mGluRs. Ghauri, M., Chapman, A.G., Meldrum, B.S. Neuroreport (1996) [Pubmed]
  16. Coexpression of full-length gamma-aminobutyric acid(B) (GABA(B)) receptors with truncated receptors and metabotropic glutamate receptor 4 supports the GABA(B) heterodimer as the functional receptor. Sullivan, R., Chateauneuf, A., Coulombe, N., Kolakowski, L.F., Johnson, M.P., Hebert, T.E., Ethier, N., Belley, M., Metters, K., Abramovitz, M., O'Neill, G.P., Ng, G.Y. J. Pharmacol. Exp. Ther. (2000) [Pubmed]
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