Direct interaction of N-ethylmaleimide-sensitive factor with GABAA receptor β subunits

GABAA receptors mediate most of the fast inhibitory neurotransmission in the brain, and are believed to be composed mainly of α, β, and γ subunits. It has been shown that GABAA receptors interact with a number of binding partners that act to regulate both receptor function and cell surface stability. Here, we reveal that GABAA receptors interact directly with N-ethylmaleimide-sensitive factor (NSF), a critical regulator of vesicular dependent protein trafficking, as measured by in vitro protein binding and co-immunoprecipitation assays. In addition, we established that NSF interacts with residues 395-415 of the receptor β subunits and co-localizes with GABAA receptors in hippocampal neurons. We also established that NSF can regulate GABAA receptor cell surface expression depending upon residues 395-415 in the β3 subunit. Together, our results suggest an important role for NSF activity in regulating the cell surface stability of GABAA receptors.