GABA receptor: Difference between revisions

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GABA receptors are proteins utilized for the primary inhibitory neurotransmitter in vertebrate central nervous systems, gamma-aminobutyric acid or GABA (Kerr, 1995). GABA has been found to be formed using the synthesizing enzyme, L-glutamic acid carboxylase, or GAD (Lloyd, 1983). Additionally, GABA has found to be synthesized via the excitatory neurotransmitter glutamate. GABA receptors regulate synaptic transmission via the opening of ion channels, causing membrane hyperpolarization and the inhibition of further signal transmission.

== Structure ==

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).  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 and the active state which has the agonist bound (Geng, 2013). Geng et. al. has found, using the GABAB crystal structures, that both subunits exist in open conformations while at rest. Upon binding with the agonist, the GABAB1 subunit closes via agonist-induced receptor activation (Geng, 2013). 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). There are two GABAB1 isoforms that differ at the N-termini where there are two sushi motifs (Cryan, 2005).