mGluR7

mGluR7, or metabotropic glutamate receptor 7, is a group III member of the metabotropic glutamate receptor family. It is a class C G-protein-coupled receptor encoded by the GRM7 gene in humans. Like other mGluRs, mGluR7 forms functional dimers and is predominantly located presynaptically in the CNS, where it modulates neurotransmission.

Structure and signaling: mGluR7 has the seven transmembrane domains and an extracellular Venus flytrap domain that binds glutamate. It couples to Gi/o proteins, inhibiting adenylyl cyclase and reducing cAMP. Through Gi/o signaling it can modulate calcium channels and vesicle release, thereby decreasing presynaptic neurotransmitter release. It has relatively low affinity for glutamate, activating mainly at high synaptic concentrations to limit excitation.

Localization and function: Expression is notable in the hippocampus, amygdala, cerebellum, and cortex. Functionally, mGluR7 acts as a presynaptic autoreceptor to constrain glutamate release and influence synaptic plasticity. Animal studies link mGluR7 signaling to anxiety-like behavior and fear conditioning, though results vary by circuit and experimental context.

Pharmacology and clinical relevance: mGluR7 is the subject of research on allosteric modulators. Both positive and negative allosteric modulators have been described, but none are approved for clinical use. Preclinical work explores mGluR7 as a potential target for anxiety disorders, epilepsy, addiction, and other CNS conditions, while emphasizing the need for selective compounds and safety assessments.

Genetics and research status: Human GRM7 variants have been studied for associations with neuropsychiatric conditions, but findings are inconclusive. Ongoing basic research aims to clarify mGluR7's precise roles in physiology and disease.