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

• This differential localisation suggests a regulation of synaptic transmission via a target cell-dependent synaptic segregation of mGluR4.Our results demonstrate that, like other group III mGluRs, presynaptic mGluR4 is highly enriched in the active zone of boutons innervating specific classes of neurones [8].
• Because the arousing or stimulant effects of ethanol seem to be relevant behavioral traits associated with its rewarding properties and genetic susceptibility to alcoholism, we addressed the role of mGluR4 by studying behavioral actions of ethanol in mutant mice lacking mGluR4 [5].
• We conclude that mGluR4 contributes substantially to the high-affinity binding site for [3H]L-AP4 in several regions of mouse brain, including cerebellar cortex, nucleus basalis, thalamus, superior colliculus, substantia nigra, and hippocampal dentate gyrus [9].
• Domain mapping revealed that alternative splicing of mGluR4, mGluR7 and mGluR8 C-termini regulated the interaction [10].
• A refined localization of mGluR4 was carried out by constructing a bacterial artificial chromosome clone contig of the region surrounding the gene [11].

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].

References