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JCS:电压门控钠离子通道研究进展

来源:中国科学院上海生命科学研究院 2008-10-17 15:56

10月1日《细胞科学杂志》(Journal of Cell Science)发表了中科院上海生科院生化与细胞所鲍岚研究组的最新研究成果:电压门控钠离子通道的3亚单位通过掩盖Nav1.8内质网滞留信号增加通道在细胞膜表面的表达量。

电压门控钠离子通道是可兴奋细胞产生动作电位的基础,Nav1.8是特异性高表达在背根神经节初级感觉小神经元中的一种电压门控钠离子通道,它与疼痛的产生有密切的关系。在这项工作中,鲍岚研究组的博士研究生张振宁和李乾等发现Nav1.8主要驻留在内质网中,其第一个胞内环上的RRR结构域是一个内质网滞留信号,对Nav1.8驻留在内质网中有贡献,限制了其有效地向细胞膜表面的运输及功能的行使。当Nav1.8的RRR内质网滞留信号失去功能后,其细胞膜表面表达量较野生型Nav1.8显著升高。电压门控钠离子通道的β3亚单位通过与Nav1.8的第一个胞内环结合,掩盖了Nav1.8的内质网滞留信号,促进Nav1.8向细胞膜表面的运输。上述工作首次在Nav1.8中发现了内质网滞留信号,并对Nav1.8中内质网滞留信号的功能与调控提供了有力的证据,同时也揭示了电压门控钠离子通道β亚单位对α亚单位调控的分子机制,为深入了解疼痛的产生和发展提供了新的研究方向和理论基础。(生物谷Bioon.com)

生物谷推荐原始出处:

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.

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