10月1日《細胞科學雜志》（Journal of Cell Science）發(fā)表了中科院上海生科院生化與細胞所鮑嵐研究組的最新研究成果：電壓門控鈉離子通道的3亞單位通過掩蓋Nav1.8內(nèi)質(zhì)網(wǎng)滯留信號增加通道在細胞膜表面的表達量,。
電壓門控鈉離子通道是可興奮細胞產(chǎn)生動作電位的基礎(chǔ),，Nav1.8是特異性高表達在背根神經(jīng)節(jié)初級感覺小神經(jīng)元中的一種電壓門控鈉離子通道，它與疼痛的產(chǎn)生有密切的關(guān)系,。在這項工作中,，鮑嵐研究組的博士研究生張振寧和李乾等發(fā)現(xiàn)Nav1.8主要駐留在內(nèi)質(zhì)網(wǎng)中，其第一個胞內(nèi)環(huán)上的RRR結(jié)構(gòu)域是一個內(nèi)質(zhì)網(wǎng)滯留信號,，對Nav1.8駐留在內(nèi)質(zhì)網(wǎng)中有貢獻,，限制了其有效地向細胞膜表面的運輸及功能的行使,。當Nav1.8的RRR內(nèi)質(zhì)網(wǎng)滯留信號失去功能后，其細胞膜表面表達量較野生型Nav1.8顯著升高,。電壓門控鈉離子通道的β3亞單位通過與Nav1.8的第一個胞內(nèi)環(huán)結(jié)合,，掩蓋了Nav1.8的內(nèi)質(zhì)網(wǎng)滯留信號，促進Nav1.8向細胞膜表面的運輸,。上述工作首次在Nav1.8中發(fā)現(xiàn)了內(nèi)質(zhì)網(wǎng)滯留信號,，并對Nav1.8中內(nèi)質(zhì)網(wǎng)滯留信號的功能與調(diào)控提供了有力的證據(jù)，同時也揭示了電壓門控鈉離子通道β亞單位對α亞單位調(diào)控的分子機制,，為深入了解疼痛的產(chǎn)生和發(fā)展提供了新的研究方向和理論基礎(chǔ)。（生物谷Bioon.com）
生物谷推薦原始出處：
Journal of Cell Science,，121, 3243-3252,，Zhen-Ning Zhang，Lan Bao
The voltage-gated Na+ channel Nav1.8 contains an ER-retention/retrieval signal antagonized by the β3 subunit
Zhen-Ning Zhang*, Qian Li*, Chao Liu, Hai-Bo Wang, Qiong Wang and Lan Bao
Laboratory of Molecular Cell Biology, Institute of Biochemistry and Cell Biology, Shanghai Institutes for Biological Sciences, Chinese Academy of Sciences, 320 Yue Yang Road, Shanghai 200031, People's Republic of China
Voltage-gated Na+ channel (Nav) 1.8 contributes to the majority of the Na+ current that underlies the depolarizing phase of action potentials. Nav1.8 is mainly distributed intracellularly and its current amplitude can be enhanced by the β3 subunit. However, little is known about the mechanisms underlying its intracellular retention and the effects mediated by the β3 subunit. Here, we show that the β3 subunit promotes surface expression of Nav1.8 by masking its endoplasmic reticulum (ER)-retention/retrieval signal. The RRR motif in the first intracellular loop of Nav1.8 is responsible for retaining Nav1.8 in the ER and restricting its surface expression. The β3 subunit facilitates surface expression of Nav1.8. The intracellular C-terminus of the β3 subunit interacts with the first intracellular loop of Nav1.8 and masks the ER-retention/retrieval signal. Mutation of the RRR motif results in a significant increase in surface expression of Nav1.8 and abolishes the β3-subunit-mediated effects. Thus, the β3 subunit regulates surface expression of Nav1.8 by antagonizing its ER-retention/retrieval signal. These results reveal a novel mechanism for the effect of the Na+ channel β subunits on the subunits.
