Goto Hidefumi, Terunuma Miho, Kanematsu Takashi, Misumi Yoshio, Moss Stephen J, Hirata Masato
Laboratory of Molecular and Cellular Biochemistry, Faculty of Dental Science and Station for Collaborative Research, Kyushu University, Fukuoka 812-8582, Japan.
Mol Cell Neurosci. 2005 Oct;30(2):197-206. 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 alpha, beta, and gamma 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 beta 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 beta3 subunit. Together, our results suggest an important role for NSF activity in regulating the cell surface stability of GABA(A) receptors.
GABA(A)受体介导大脑中大部分快速抑制性神经传递，据信主要由α、β和γ亚基组成。研究表明，GABA(A)受体与许多结合伴侣相互作用，这些结合伴侣可调节受体功能和细胞表面稳定性。在此，我们通过体外蛋白质结合和共免疫沉淀试验发现，GABA(A)受体直接与N-乙基马来酰亚胺敏感因子（NSF）相互作用，NSF是囊泡依赖性蛋白质运输的关键调节因子。此外，我们证实NSF与受体β亚基的395-415位残基相互作用，并与海马神经元中的GABA(A)受体共定位。我们还证实，NSF可根据β3亚基中的395-415位残基调节GABA(A)受体的细胞表面表达。总之，我们的结果表明NSF活性在调节GABA(A)受体的细胞表面稳定性中起重要作用。
