title: Endophilin A2 Influences Volume-Regulated Chloride Current by Mediating ClC-3 Trafficking in Vascular Smooth Muscle Cells.
abstract: Previous research has demonstrated that ClC-3 is responsible for volume-regulated Cl-current (ICl.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 ofICl.vol.
  
  
  
  Volume-regulated chloride current (ICl.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 increaseICl.vol, while endophilin A2 knockdown decreasedICl.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.
  
  
  
  The present study identified endophilin A2 as a ClC-3 channel partner, which serves as a new ClC-3 trafficking insight in regulatingICl.volin 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. (Circ J 2016; 80: 2397-2406).
authors.affiliation: Department of Pharmacology, Zhongshan School of Medicine, Sun Yat-sen University.
authors.forename: Can-Zhao
authors.initials: CZ
authors.lastname: Liu
authors.forename: Xiang-Yu
authors.initials: XY
authors.lastname: Li
authors.forename: Ren-Hong
authors.initials: RH
authors.lastname: Du
authors.forename: Min
authors.initials: M
authors.lastname: Gao
authors.forename: Ming-Ming
authors.initials: MM
authors.lastname: Ma
authors.forename: Fei-Ya
authors.initials: FY
authors.lastname: Li
authors.forename: Er-Wen
authors.initials: EW
authors.lastname: Huang
authors.forename: Hong-Shuo
authors.initials: HS
authors.lastname: Sun
authors.forename: Guan-Lei
authors.initials: GL
authors.lastname: Wang
authors.forename: Yong-Yuan
authors.initials: YY
authors.lastname: Guan
mesh_terms: D000217:Acyltransferases / Q000235:genetics / Q000378:metabolism*; D000818:Animals; D002462:Cell Membrane / Q000235:genetics / Q000378:metabolism*; D018118:Chloride Channels / Q000235:genetics / Q000378:metabolism*; D002712:Chlorides / Q000378:metabolism*; D017136:Ion Transport; D008564:Membrane Potentials; D051379:Mice; D018345:Mice, Knockout; D009131:Muscle, Smooth, Vascular / Q000378:metabolism*; D032389:Myocytes, Smooth Muscle / Q000378:metabolism*; D021381:Protein Transport
chemical_list: D018118:Chloride Channels; D002712:Chlorides; C115376:ClC-3 channel; D000217:Acyltransferases; C018764:2-acylglycerophosphate acyltransferase