Document Detail

Calreticulin positively regulates the expression and function of epithelial sodium channel.
MedLine Citation:
PMID:  19799896     Owner:  NLM     Status:  MEDLINE    
Epithelial sodium channel (ENaC) is a heteromultimeric Na(+) channel at the apical membrane in the kidney, colon, and lung. Because ENaC plays a crucial role in regulating Na(+) absorption and extracellular fluid volume, its dysregulation causes severe phenotypes including hypertension, hypokalemia, and airway obstruction. Despite the importance of ENaC, its protein quality control mechanism remains less established. Here we firstly show the role of calreticulin (CRT), a lectin-like molecular chaperone in the endoplasmic reticulum (ER), on the regulation of ENaC. Overexpression and knockdown analyses clearly indicated that CRT positively affects the expression of each ENaC subunit (alpha, beta and gamma). CRT overexpression also up-regulated the cell surface expression of alpha-, beta- and gamma-ENaC. Moreover, we found that CRT directly interacts with each ENaC subunit. Although CRT knockdown did not affect the de novo synthesis of ENaC subunits, CRT overexpression decreased alpha-, beta- and gamma-ENaC expression in the detergent (RIPA)-insoluble fraction, suggesting that CRT enhanced the solubility of ENaC subunits. Consistent with the increased intracellular and cell surface expression of ENaC subunits, increased channel activity of ENaC was also observed upon overexpression of CRT. Our study thus identifies CRT as an ER chaperone that regulates ENaC expression and function.
Takuya Sugahara; Tomoaki Koga; Keiko Ueno-Shuto; Tsuyoshi Shuto; Eriko Watanabe; Ai Maekawa; Kenichiro Kitamura; Kimio Tomita; Ai Mizuno; Takashi Sato; Mary Ann Suico; Hirofumi Kai
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Publication Detail:
Type:  Journal Article; Research Support, Non-U.S. Gov't     Date:  2009-09-30
Journal Detail:
Title:  Experimental cell research     Volume:  315     ISSN:  1090-2422     ISO Abbreviation:  Exp. Cell Res.     Publication Date:  2009 Nov 
Date Detail:
Created Date:  2009-11-02     Completed Date:  2010-01-19     Revised Date:  -    
Medline Journal Info:
Nlm Unique ID:  0373226     Medline TA:  Exp Cell Res     Country:  United States    
Other Details:
Languages:  eng     Pagination:  3294-300     Citation Subset:  IM    
Department of Molecular Medicine, Graduate School of Pharmaceutical Sciences, Kumamoto University, Kumamoto, Japan.
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MeSH Terms
CHO Cells
Calreticulin / genetics,  pharmacology*
DNA, Complementary
Endoplasmic Reticulum
Epithelial Sodium Channel / genetics*,  metabolism,  physiology
Gene Expression Regulation / drug effects*
Molecular Chaperones
Protein Binding
Protein Subunits
Reg. No./Substance:
0/Calreticulin; 0/DNA, Complementary; 0/Epithelial Sodium Channel; 0/Molecular Chaperones; 0/Protein Subunits

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