Epithelial sodium channels are activated by furin-dependent proteolysis

被引:348
作者
Hughey, RP
Bruns, JB
Kinlough, CL
Harkleroad, KL
Tong, QS
Carattino, MD
Johnson, JP
Stockand, JC
Kleyman, TR
机构
[1] Univ Pittsburgh, Sch Med, Dept Med, Renal Electrolyte Div, Pittsburgh, PA 15261 USA
[2] Univ Texas, Hlth Sci Ctr, Dept Physiol, San Antonio, TX 78229 USA
关键词
D O I
10.1074/jbc.C400080200
中图分类号
Q5 [生物化学]; Q7 [分子生物学];
学科分类号
071010 ; 081704 ;
摘要
Epithelial Na+ channels (ENaCs) are activated by extracellular trypsin or by co-expression with channel-activating proteases, although there is no direct evidence that these proteases activate ENaC by cleaving the channel. We previously demonstrated that the alpha and gamma subunits of ENaC are cleaved during maturation near consensus sites for furin cleavage. Using site-specific mutagenesis of channel subunits, ENaC expression in furin-deficient cells, and furin-specific inhibitors, we now report that ENaC cleavage correlates with channel activity. Channel activity in furin-deficient cells was rescued by expression of furin. Our data provide the first example of a vertebrate ion channel that is a substrate for furin and whose activity is dependent on its proteolysis.
引用
收藏
页码:18111 / 18114
页数:4
相关论文
共 39 条
[1]   Clathrin-mediated endocytosis of MUC1 is modulated by its glycosylation state [J].
Altschuler, Y ;
Kinlough, CL ;
Poland, PA ;
Bruns, JB ;
Apodaca, G ;
Weisz, OA ;
Hughey, RP .
MOLECULAR BIOLOGY OF THE CELL, 2000, 11 (03) :819-831
[2]  
Bens M, 1999, J AM SOC NEPHROL, V10, P923
[3]   A region directly following the second transmembrane domain in γENaC is required for normal channel gating [J].
Booth, RE ;
Tong, QS ;
Medina, J ;
Snyder, PM ;
Patel, P ;
Stockand, JD .
JOURNAL OF BIOLOGICAL CHEMISTRY, 2003, 278 (42) :41367-41379
[4]   Na+ transport in normal and CF human bronchial epithelial cells is inhibited by BAY 39-9437 [J].
Bridges, RJ ;
Newton, BB ;
Pilewski, JM ;
Devor, DC ;
Poll, CT ;
Hall, RL .
AMERICAN JOURNAL OF PHYSIOLOGY-LUNG CELLULAR AND MOLECULAR PHYSIOLOGY, 2001, 281 (01) :L16-L23
[5]   Multiple epithelial Na+ channel domains participate in subunit assembly [J].
Bruns, JB ;
Hu, BF ;
Ahn, YJ ;
Sheng, SH ;
Hughey, RP ;
Kleyman, TR .
AMERICAN JOURNAL OF PHYSIOLOGY-RENAL PHYSIOLOGY, 2003, 285 (04) :F600-F609
[6]   Serine protease activation of near-silent epithelial Na+ channels [J].
Caldwell, RA ;
Boucher, RC ;
Stutts, MJ .
AMERICAN JOURNAL OF PHYSIOLOGY-CELL PHYSIOLOGY, 2004, 286 (01) :C190-C194
[7]   Protease modulation of the activity of the epithelial sodium channel expressed in Xenopus oocytes [J].
Chraïbi, A ;
Vallet, V ;
Firsov, D ;
Hess, SK ;
Horisberger, JD .
JOURNAL OF GENERAL PHYSIOLOGY, 1998, 111 (01) :127-138
[8]   BMP-4 is proteolytically activated by furin and/or PC6 during vertebrate embryonic development [J].
Cui, YZ ;
Jean, F ;
Thomas, G ;
Christian, JL .
EMBO JOURNAL, 1998, 17 (16) :4735-4743
[9]   Regulation of the epithelial sodium channel by serine proteases in human airways [J].
Donaldson, SH ;
Hirsh, A ;
Li, DC ;
Holloway, G ;
Chao, J ;
Boucher, RC ;
Gabriel, SE .
JOURNAL OF BIOLOGICAL CHEMISTRY, 2002, 277 (10) :8338-8345
[10]   The heterotetrameric architecture of the epithelial sodium channel (ENaC) [J].
Firsov, D ;
Gautschi, I ;
Merillat, AM ;
Rossier, BC ;
Schild, L .
EMBO JOURNAL, 1998, 17 (02) :344-352