Gamma-aminobutyric acid receptor subunit B (GABAB2) (GABAB2)

The gamma-aminobutyric acid receptor subunit B, commonly known as GABAB2 or the R2 subunit, forms an obligate heterodimer with the GABAB1 (R1) subunit to create the functional metabotropic GABAB receptor, a class C G protein-coupled receptor (GPCR) that mediates slow inhibitory neurotransmission in the central nervous system. GABAB2 contains an extracellular Venus flytrap domain connected via a unique stalk to a seven-transmembrane domain, with its C-terminus facilitating heterodimerization through a coiled-coil motif and G protein coupling primarily via Gi/o proteins, which inhibit adenylyl cyclase and modulate ion channels like GIRK and voltage-gated calcium channels. This subunit is essential for trafficking the heterodimer to the plasma membrane, as GABAB1 alone is retained in the endoplasmic reticulum, and it hosts allosteric binding sites for positive modulators within the transmembrane domain interface. GABAB receptors, including GABAB2, are implicated in various neurological diseases due to their roles in modulating neuronal excitability presynaptically and postsynaptically. Drugs like baclofen act as orthosteric agonists binding to GABAB1 but require GABAB2 for downstream signaling, while allosteric modulators like GS39783 enhance receptor activity at the GABAB2-involved sites, offering therapeutic potential in conditions such as spasticity, addiction, and pain.

Other names

GABA_B2GABAB R2GBR2R2 subunit

Metabotropic receptor agonist at orthosteric site in Venus flytrap domain of GABAB1 (with GABAB2 required for functional signaling), Positive allosteric modulation at transmembrane domain interface