Family

GPCR, family 3, metabotropic glutamate receptor 8 (IPR000144)

Short name: GPCR_3_mtglu_rcpt_8

Family relationships

Description

G protein-coupled receptors (GPCRs) constitute a vast protein family that encompasses a wide range of functions, including various autocrine, paracrine and endocrine processes. They show considerable diversity at the sequence level, on the basis of which they can be separated into distinct groups [PMID: 12679517]. The term clan can be used to describe the GPCRs, as they embrace a group of families for which there are indications of evolutionary relationship, but between which there is no statistically significant similarity in sequence [PMID: 8170923]. The currently known clan members include rhodopsin-like GPCRs (Class A, GPCRA), secretin-like GPCRs (Class B, GPCRB), metabotropic glutamate receptor family (Class C, GPCRC), fungal mating pheromone receptors (Class D, GPCRD), cAMP receptors (Class E, GPCRE) and frizzled/smoothened (Class F, GPCRF) [PMID: 8170923, PMID: 8081729, PMID: 15914470, PMID: 18948278, PMID: 16753280]. GPCRs are major drug targets, and are consequently the subject of considerable research interest. It has been reported that the repertoire of GPCRs for endogenous ligands consists of approximately 400 receptors in humans and mice [PMID: 12679517]. Most GPCRs are identified on the basis of their DNA sequences, rather than the ligand they bind, those that are unmatched to known natural ligands are designated by as orphan GPCRs, or unclassified GPCRs [PMID: 23020293].

GPCR family 3 receptors (also known as family C) are structurally similar to other GPCRs, but do not show any significant sequence similarity and thus represent a distinct group. Structurally they are composed of four elements; an N-terminal signal sequence; a large hydrophilic extracellular agonist-binding region containing several conserved cysteine residues which could be involved in disulphide bonds; a shorter region containing seven transmembrane domains; and a C-terminal cytoplasmic domain of variable length [PMID: 17266540]. Family 3 members include the metabotropic glutamate receptors, the extracellular calcium-sensing receptors, the gamma-amino-butyric acid (GABA) type B receptors, and the vomeronasal type-2 receptors [PMID: 1309649, PMID: 8255296, PMID: 10773016, PMID: 9292726]. As these receptors regulate many important physiological processes they are potentially promising targets for drug development.

The metabotropic glutamate receptors are functionally and pharmacologically distinct from the ionotropic glutamate receptors. They are coupled to G-proteins and stimulate the inositol phosphate/Ca2+ intracellular signalling pathway [PMID: 1847995, PMID: 1656524, PMID: 1320017, PMID: 1309649]. At least eight sub-types of metabotropic receptor (MGR1-8) have been identified in cloning studies. The sub-types differ in their agonist pharmacology and signal transduction pathways.

MGR8 has a strong expression in olfactory bulb, pontine gray, lateral reticular nucleus of the thalamus, and piriform cortex; less abundant expression has been detected in cerebral cortex, hippocampus, cerebellum, mammillary body and retina [PMID: 7722646, PMID: 9016353]. Glutamate evokes pertussis toxin-sensitive potassium currents in Xenopus laevis oocytes co-expressing MGR8 and G-protein-coupled inwardly rectifying potassium channels [PMID: 9016353]. The pharmacology and expression of MGR8 in mitral/tufted cells suggest it could be a presynaptic receptor modulating glutamate release by these cells at their axon terminals in the entorhinal cortex [PMID: 7722646].

GO terms

Biological Process

GO:0007186 G-protein coupled receptor signaling pathway

Molecular Function

No terms assigned in this category.

Cellular Component

GO:0016021 integral component of membrane

Contributing signatures

Signatures from InterPro member databases are used to construct an entry.
PRINTS