Nuclear Factor-kappaB Gates Na(v)1.7 Channels in DRG Neurons via Protein-Protein Interaction
Nuclear Factor-kappaB Gates Na(v)1.7 Channels in DRG Neurons via Protein-Protein Interaction
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核因子-kappaB 通过蛋白质-蛋白质相互作用控制 DRG 神经元中的 Na(v)1.7 通道
DOI：
10.1016/j.isci.2019.08.017
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发表时间：
2019
期刊：
影响因子：
5.8
通讯作者：
Liu Xian-Guo
中科院分区：
文献类型：
--
作者：
Xie Man-Xiu;Zhang Xiao-Long;Xu Jing;Zeng Wei-An;Li Dai;Xu Ting;Pang Rui-Ping;Ma Ke;Liu Xian-Guo
核因子-κ B（NF-κB）通过核转录调节神经元的结构和功能。本研究表明，NF-κB B亚基的活性形式磷酸化p65（p-p65）与大鼠背根神经节（DRG）神经元膜上的Nav1.7通道可逆地相互作用。这种相互作用通过减慢Nav1.7通道的失活并促进其从失活中恢复来增加Nav1.7电流，这可能增加了准备激活的通道的静息状态。在培养的DRG神经元中，TNF-α在5 min内上调膜p65和Nav1.7电流，但在40 min内不影响核NF-κB B。这种对Nav1.7的非转录作用可能是快速调节躯体感觉系统敏感性的基础。NF-κB和Nav1.7通道都与许多生理功能和疾病密切相关。我们的发现可能为研究潜在机制提供新的线索。
It is well known that nuclear factor-kappaB (NF-κB) regulates neuronal structures and functions by nuclear transcription. Here, we showed that phospho-p65 (p-p65), an active form of NF-κB subunit, reversibly interacted with Nav1.7 channels in the membrane of dorsal root ganglion (DRG) neurons of rats. The interaction increased Nav1.7 currents by slowing inactivation of Nav1.7 channels and facilitating their recovery from inactivation, which may increase the resting state of the channels ready for activation. In cultured DRG neurons TNF-α upregulated the membranep-p65 and enhanced Nav1.7 currents within 5 min but did not affect nuclear NF-κB within 40 min. This non-transcriptional effect on Nav1.7 may underlie a rapid regulation of the sensibility of the somatosensory system. Both NF-κB and Nav1.7 channels are critically implicated in many physiological functions and diseases. Our finding may shed new light on the investigation into the underlying mechanisms.