Insulin-stimulated trafficking of ENaC in renal cells requires PI 3-kinase activity

被引:86
作者
Blazer-Yost, BL
Esterman, MA
Vlahos, CJ
机构
[1] Indiana Univ Purdue Univ, Dept Biol, Indianapolis, IN 46202 USA
[2] Eli Lilly & Co, Lilly Res Labs, Therapeut Area Discovery Res, Indianapolis, IN 46285 USA
[3] Eli Lilly & Co, Lilly Res Labs, Chem Informat Technol, Indianapolis, IN 46285 USA
[4] Eli Lilly & Co, Lilly Res Labs, Cardiovasc Res, Indianapolis, IN 46285 USA
来源
AMERICAN JOURNAL OF PHYSIOLOGY-CELL PHYSIOLOGY | 2003年 / 284卷 / 06期
关键词
epithelial sodium channels; phosphatidylinositol 3,4,5-bisphosphate; phosphatidylinositol; 3-kinase; phosphoinositide pathway; transepithelial signal transduction; sodium transport;
D O I
10.1152/ajpcell.00372.2002
中图分类号
Q2 [细胞生物学];
学科分类号
071009 ; 090102 ;
摘要
alphaENaC-EGFP (enhanced green fluorescent protein-tagged alpha-subunit of the epithelial Na+ channel) stably transfected clonal lines derived from the A6 parental cell line were used to study the physical mechanisms of insulin-stimulated Na+ transport. Within 1 min of insulin stimulation, ENaC migrates from a diffuse cytoplasmic localization to the apical and lateral membranes. Concurrently, after insulin stimulation, phosphatidylinositol 3-kinase (PI 3-kinase) is colocalized with ENaC on the lateral but not apical membrane. An inhibitor of PI 3-kinase, LY-294002, does not inhibit ENaC/PI 3-kinase colocalization but does alter the intracellular site of the colocalization, preventing the translocation of ENaC to the lateral and apical membranes. These data show that insulin stimulation causes the migration of ENaC to the lateral and apical cell membranes and that this trafficking is dependent on PI 3-kinase activity.
引用
收藏
页码:C1645 / C1653
页数:9
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