Molecular Membrane Biology

GABAA receptors are the major inhibitory transmitter receptors in the central nervous system. They are chloride ion channels that can be opened by g-aminobutyric acid (GABA) and are the targets of action of a variety of pharmacologically and clinically important drugs. GABAA receptors are composed of five subunits that can belong to different subunit classes. The existence of 19 different subunits gives rise to the formation of a large variety of distinct GABAA receptor subtypes in the brain. The majority of GABAA receptors seems to be composed of two a, two b and one g subunit and the occurrence of a defined subunit stoichiometry and arrangement in abg receptors strongly indicates that assembly of GABAA receptors proceeds via defined pathways. Based on the differential ability of subunits to interact with each other, a variety of studies have been performed to identify amino acid sequences or residues important for assembly. Such residues might be involved in direct protein-protein interactions, or in stabilizing direct contact sites in other regions of the subunit. Several homooligomeric or hetero-oligomeric assembly intermediates could be the starting point of GABAA receptor assembly but so far no unequivocal assembly mechanism has been identified. Possible mechanisms of assembly of GABAA receptors are discussed in the light of recent publications.