期刊
JOURNAL OF BIOLOGICAL CHEMISTRY
卷 280, 期 44, 页码 36762-36772出版社
AMER SOC BIOCHEMISTRY MOLECULAR BIOLOGY INC
DOI: 10.1074/jbc.M508944200
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资金
- NCRR NIH HHS [P20-RR018787] Funding Source: Medline
- NIDDK NIH HHS [R01-DK34533, R01-DK45881] Funding Source: Medline
The most common mutation in the cystic fibrosis transmembrane conductance regulator ( CFTR) gene in individuals with cystic fibrosis, Delta F508, causes retention of Delta F508-CFTR in the endoplasmic reticulum and leads to the absence of CFTR Cl- channels in the apical plasma membrane. Rescue of Delta F508-CFTR by reduced temperature or chemical means reveals that the Delta F508 mutation reduces the half-life of Delta F508-CFTR in the apical plasma membrane. Because Delta F508-CFTR retains some Cl- channel activity, increased expression of \Delta F508-CFTR in the apical membrane could serve as a potential therapeutic approach for cystic fibrosis. However, little is known about the mechanisms responsible for the short apical membrane half-life of Delta F508-CFTR in polarized human airway epithelial cells. Accordingly, the goal of this study was to determine the cellular defects in the trafficking of rescued Delta F508-CFTR that lead to the decreased apical membrane half-life of Delta F508-CFTR in polarized human airway epithelial cells. We report that in polarized human airway epithelial cells (CFBE41o-) the Delta F508 mutation increased endocytosis of CFTR from the apical membrane without causing a global endocytic defect or affecting the endocytic recycling of CFTR in the Rab11a-specific apical recycling compartment.
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