GABA receptor: Difference between revisions

GABA receptors are proteins utilized for the primary inhibitory neurotransmitter in vertebrate central nervous systems, gamma-aminobutyric acid or GABA (Kerr, 1995). Upon binding with GABA, GABAB receptors utilize a second messenger amplification pathway that ultimately results in the inhibitory signal for neuronal transmission. This pathway for signal transmission differs from GABAA receptors, which are considered ligand-gated ion channels as the binding of GABA results in the opening of ion channels leading to the inhibition of a neuronal signal.  

There are two major classes of GABA receptors abundant throughout neuronal cell types, ionotropic and metabotropic (Cryan, 2005). Metabotropic GABAB receptors are a specific division of the GABA receptor (Kerr, 1995). The GABAB receptor functions as a heterodimer of two subunits, GABAB1  and GABAB2. Heterodimerization is accomplished using coiled-coil motifs within the C-termini and interactions between the transmembrane and extracellular domains (Cryan, 2005). Additionally, there are two GABAB1 isoforms that differ at the N-termini where there are two sushi domains (Cryan, 2005). These sushi domains on the GABAB1 subunit is key to the receptor's interaction with other proteins as well as axonal signaling (Cryan, 2005). GABAB1, a seven-transmembrane spanning protein receptor was identified first using an expression cloning technique using radiolabeled iodinated receptor ligands. The GABAB1 subunit has a molecular weight of 130 kDa. It is not expressed on the cell surface without the help of the seven transmembrane spanning motif GABAB2. GABAB2 links to GABAB1 at the endoplasmic reticulum via their intracellular C-terminus to form the heterodimer GABAB receptor (Sigma Aldrich).  The GABAB receptor exists in two different forms - in the resting state (i.e. unbound state) and the active state (i.e. bound state)(Geng, 2013). Geng et. al. has found, using the GABAB crystal structures, that both subunits exist in open conformations while at rest (see above). Upon binding with the agonist, the GABAB1 subunit closes(Geng, 2013) (see below). Additionally, it was found that the agonist is bound in the interdomain crevice of the GABAB1 subunit due to an overlap of amino acid residues (Geng, 2013).