Endophilin A2 Influences Volume-Regulated Chloride Current by Mediating ClC-3 Trafficking in Vascular Smooth Muscle Cells
Endophilin A2 Influences Volume-Regulated Chloride Current by Mediating ClC-3 Trafficking in Vascular Smooth Muscle Cells
复制标题
内亲素 A2 通过介导血管平滑肌细胞中的 ClC-3 运输来影响容量调节的氯电流
DOI：
10.1253/circj.cj-16-0793
复制
发表时间：
2016-11-01
影响因子：
3.3
通讯作者：
Guan, Yong-Yuan
中科院分区：
文献类型：
--
作者：
Liu, Can-Zhao;Li, Xiang-Yu;Guan, Yong-Yuan
Background: Previous research has demonstrated that ClC-3 is responsible for volume-regulated Cl-current (I-Cl.vol) in vascular smooth muscle cells (VSMCs). However, it is still not clear whether and how ClC-3 is transported to cell membranes, resulting in alteration of I-Cl.vol.Methods and Results: Volume-regulated chloride current (I-Cl.vol) was recorded by whole-cell patch clamp recording, and Western blotting and co-immunoprecipitation were performed to examine protein expression and protein-protein interaction. Live cell imaging was used to observe ClC-3 transporting. The results showed that an overexpression of endophilin A2 could increase I-Cl.vol, while endophilin A2 knockdown decreased I-Cl.vol. In addition, the SH3 domain of endophilin A2 mediated its interaction with ClC-3 and promotes ClC-3 transportation from the cytoplasm to cell membranes. The regulation of ClC-3 channel activity was also verified in basilar arterial smooth muscle cells (BASMCs) isolated from endophilin A2 transgenic mice. Moreover, endophilin A2 increase VSMCs proliferation induced by endothelin-1 or hypo-osmolarity.Conclusions: The present study identified endophilin A2 as a ClC-3 channel partner, which serves as a new ClC-3 trafficking insight in regulating I-Cl.vol in VSMCs. This study provides a new mechanism by which endophilin A2 regulates ClC-3 channel activity, and sheds light on how ClC-3 is transported to cell membranes to play its critical role as a chloride channel in VSMCs function, which may be involved in cardiovascular diseases.
