Open AccessDirect interactions between EN aC gamma subunit and Cl CN 2 in cystic fibrosis epithelial cells
Author(s) -
Henry Katherine R.,
Lee Seakwoo,
Walker Douglas,
Zeitlin Pamela L.
Publication year - 2015
Publication title -
physiological reports
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 0.918
H-Index - 39
ISSN - 2051-817X
DOI - 10.14814/phy2.12264
Subject(s) - epithelial sodium channel , cystic fibrosis , chloride channel , downregulation and upregulation , chemistry , protein subunit , microbiology and biotechnology , cystic fibrosis transmembrane conductance regulator , secretion , biology , cancer research , medicine , sodium , gene , biochemistry , organic chemistry
Cystic fibrosis ( CF ) is a lethal disease caused by mutations in the chloride channel CFTR gene. The disease is characterized by decreased chloride secretion and unregulated sodium absorption through the epithelial sodium channel ( EN aC) in the airway epithelium and other affected organs. We hypothesize that a non‐ CFTR alternative chloride channel Cl CN 2 can be activated to negatively regulate EN aC in CF epithelial cell cultures. We identified a novel interaction between Cl CN 2 and the EN aC γ subunit in CF airway epithelial cells and show that the upregulation of Cl CN 2 leads to decreased expression of EN aC γ via a K63 ubiquitination mechanism. These regulatory effects of Cl CN 2 on EN aC γ appear to be dependent on the CBS ‐1 domain located within the c‐terminus of Cl CN 2, which is necessary for the targeting of Cl CN 2 to the apical surface. In sum, these results suggest the ability of Cl CN 2 to negatively regulate sodium absorption through EN aC, supporting its role as a therapeutic target for the treatment of CF .