The voltage-gated Na+ channel Nav1.8 contains an ER-retention/retrieval signal antagonized by the β3 subunit

被引：43

作者：

Zhang, Zhen-Ning ^{[1
]}

Li, Qian ^{[1
]}

Liu, Chao ^{[1
]}

Wang, Hai-Bo ^{[1
]}

Wang, Qiong ^{[1
]}

Bao, Lan ^{[1
]}

机构：

[1] Chinese Acad Sci, Shanghai Inst Biol Sci, Inst Biochem & Cell Biol, Mol Cell Biol Lab, Shanghai 200031, Peoples R China

来源：

JOURNAL OF CELL SCIENCE | 2008年 / 121卷 / 19期

基金：

中国国家自然科学基金;

关键词：

Na(v)1.8; ER-retention/retrieval signal; Na+ channel beta 3 subunit;

D O I：

10.1242/jcs.026856

中图分类号：

Q2 [细胞生物学];

学科分类号：

071009 ; 090102 ;

摘要：

Voltage-gated Na+ channel (Na-v) 1.8 contributes to the majority of the Na+ current that underlies the depolarizing phase of action potentials. Na(v)1.8 is mainly distributed intracellularly and its current amplitude can be enhanced by the beta 3 subunit. However, little is known about the mechanisms underlying its intracellular retention and the effects mediated by the beta 3 subunit. Here, we show that the beta 3 subunit promotes surface expression of Na(v)1.8 by masking its endoplasmic reticulum (ER)-retention/retrieval signal. The RRR motif in the first intracellular loop of Nav1.8 is responsible for retaining Na(v)1.8 in the ER and restricting its surface expression. The beta 3 subunit facilitates surface expression of Na(v)1.8. The intracellular C-terminus of the beta 3 subunit interacts with the first intracellular loop of Na(v)1.8 and masks the ER-retention/retrieval signal. Mutation of the RRR motif results in a significant increase in surface expression of Na(v)1.8 and abolishes the beta 3-subunit-mediated effects. Thus, the beta 3 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 beta subunits on the alpha subunits.

引用

页码：3243 / 3252

页数：10

共 38 条

[1] Activation of delta opioid receptors induces receptor insertion and neuropeptide secretion [J].