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

• Published in: Molecular and cellular neuroscience 2005-10, Vol.30 (2), p.197-206
• Main Authors: Goto, Hidefumi, Terunuma, Miho, Kanematsu, Takashi, Misumi, Yoshio, Moss, Stephen J., Hirata, Masato
• Format: Article
• Language: English
• Subjects: Amino Acid Sequence; Animals; Base Sequence; Cell Line; Cercopithecus aethiops; COS Cells; Humans; Kidney; Mice; Molecular Sequence Data; Mutagenesis, Site-Directed; N-Ethylmaleimide-Sensitive Proteins; Peptide Fragments - chemistry; Receptors, GABA - chemistry; Receptors, GABA - genetics; Receptors, GABA - physiology; Recombinant Fusion Proteins; Vesicular Transport Proteins - physiology
• ISSN: 1044-7431; 1095-9327
• DOI: 10.1016/j.mcn.2005.07.006

GABA A 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 GABA A receptors interact with a number of binding partners that act to regulate both receptor function and cell surface stability. Here, we reveal that GABA A 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 GABA A receptors in hippocampal neurons. We also established that NSF can regulate GABA A 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 GABA A receptors.