γ-Aminobutyric Acid Type A (GABAA) Receptor α Subunits Play a Direct Role in Synaptic Versus Extrasynaptic Targeting.
γ-Aminobutyric acid (GABA) is the main inhibitory neurotransmitter in the central nervous system of mammals. The neurotransmitter binds to the GABAA receptors and causes the membrane potential of neurons to fall and deactivate the neuron. These GABAA receptors are ligand-gated ion channel complexes made up of several subunits and can be localized along the plasma membrane either right at the synapse or far away from the synapse. Mistakes in GABAA receptor localization can lead to epilepsy, sleep disorders, and mental health problems. Earlier work had suggested that γ2 and δ subunits played a role in targeting the GABAA receptors to synaptic and extrasynaptic sites. In this Paper of the Week, a team led by Gong Chen at The Pennsylvania State University used a model neuronal system with δ/γ2 chimeras to demonstrate that the α2 and α6 subunits were involved in the subcellular targeting of GABAA receptors. The data indicated that the α subunits, along with the δ and γ2 subunits, were directly responsible for the subcellular localization of GABAA receptors as well as interactions with a critical cofactor called gephyrin. J. Biol. Chem. 2012, 287, 27417–27430