Introduction of GRM4
GRM4 (mGluR4) is encoded by the GRM4 gene localized in human chromosome 6. It is classified into group III metabotropic glutamate receptors (mGluRs) based on sequence homology, G-protein-coupling profile and ligand specificity. mGluRs are members of class C of the G-protein coupled receptors and possess a seven-transmembrane-spanning domain and an extracellular domain which contains the glutamate binding site. GRM4 is very highly expressed in the cerebellum, with lower levels of expression in the hippocampus, basal ganglia, and olfactory bulb. GRM4 is predominantly expressed presynaptically. It is commonly coupled to second messenger pathway via Gαi/o proteins that inhibit adenylylcyclase thus cAMP formation and protein kinase Aactivation in heterologous expression systems. Besides, the GRM4 receptor can also act by coupling to the Gαq protein, thus activating the phospholipase C effector system and thus excitatory events.
|Basic Information of GRM4|
|Protein Name||Metabotropic glutamate receptor 4|
|Organism||Homo sapiens (Human)|
Functions of GRM4 Membrane Protein
GRM4 has been genetically deleted in mice to study the function of this receptor. Mice lacking this receptor show impaired cerebellar synaptic plasticity and learning complicated motor tasks as well as enhanced spatial reversal learning performance. GRM4 has also been shown to modulate GABA(A) receptor-mediated seizure activity, and mGluR4–/– mice also lack motor stimulatory effects induced by ethanol. Highly selective, either orthosteric or allosteric, ligands for this receptor targeting the GRM4 for the treatment of disorders of the central nervous system (CNS) aswell as immunological (neuroinflammation) and metabolic diseases (diabetes) have been developed in recent years. For example, a highly selective GRM4 positive allosteric regulator (PAM), PHCCC, potentiates GRM4 responses at the striatopallidal synapse, and intracerebroventricular injection of PHCCC, as well as several other mGluR4 PAMs, have antiparkinsonian effects in rodent models.
Applications of GRM4 Membrane Protein in Literature
This article assessed the potential of a novel mGluR4 positive allosteric modulator (PAM), foliglurax, as an anti-parkinsonian treatment in non-human primate (NHP) models. The results showed that foliglurax can alleviate the motor symptoms of PD and the motor complications induced by levodopa.
This article examined the changes of expression of mGluR4 after diffuse brain injury (DBI) and the role of its specific agonist L-AP4 in vivo. The results showed that DBI increased the expression of mGluR4 and L-AP4 could provide neuroprotective effects against the disease.
This article investigated the relationship between mGluR2 and D2 receptor in the regulation and inhibitory control of behavior by testing the effects of a positive allosteric mGluR4 modulator, Cpd11, both alone and in combination with the D2 receptor antagonist eticlopride on impulsivity. Results showed that these two receptors play a cooperative role in modulating impulsive behavior.
This study assessed the effects of modulating mGluR4 signaling on acquisition and extinction of conditioned fear using the specific orthosteric mGluR4 agonist LSP1-2111. The results supported a role for mGluR4 signaling in the acquisition of fear learning and memory.
This article demonstrated that both mGluR1 and mGluR4 were potential drug targets to interfere with the development of hippocampal damage and seizure activity in temporal lobe epilepsy.
GRM4 Preparation Options
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