Family

GPCR family 3, gamma-aminobutyric acid receptor, type B2 (IPR002457)

Short name: GPCR_3_GABA_rcpt_B2

Family relationships

Description

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.

GABA is the principal inhibitory neurotransmitter in the brain, and signals through ionotropic (type A and type C) and metabotropic (type B) receptor systems. The type B receptors have been cloned, and photoaffinity labelling experiments suggest that they correspond to two highly conserved receptor forms in the vertebrate nervous system [PMID: 9069281]. These receptors are involved in the fine tuning of inhibitory synaptic transmission [PMID: 9844003]. Presynaptic receptors inhibit neurotransmitter release by down-regulating high-voltage activated calcium channels, while postsynaptic receptors decrease neuronal excitability by activating a prominent inwardly rectifying potassium (Kir) conductance that underlies the late inhibitory postsynaptic potentials [PMID: 9844003]. The type B receptors negatively couple to adenylyl cyclase and show sequence similarity to the metabotropic receptors for the excitatory neurotransmitter L-glutamate. The physiological form of the B receptor may be a heterodimer of the B1 and B2 subtypes [PMID: 9872316].

A new subtype of the type B receptor (type B2) has been identified by EST database mining [PMID: 9872316]. Yeast two-hybrid screening has shown that the new subtype forms heterodimers with GABA subtype B1 via an interaction at their intracellular C-terminal tails. On expression with B2 in HEK293T cells, B1 is terminally glycosylated and expressed at the cell surface. Co-expression of the receptors produces a fully functional type B receptor at the cell surface; this receptor binds GABA with a high affinity equivalent to that of the endogenous brain receptor [PMID: 9872316]. Such results indicate that, in vivo, functional brain GABA(B) receptors may be heterodimers of the B1 and B2 subtypes.

GO terms

Biological Process

GO:0007186 G-protein coupled receptor signaling pathway

Molecular Function

GO:0004965 G-protein coupled GABA receptor activity

Cellular Component

GO:0016021 integral component of membrane

Contributing signatures

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