The short apical membrane half-life of rescued ΔF508-cystic fibrosis transmembrane conductance regulator (CFTR) results from accelerated endocytosis of ΔF508H-CFTR in polarized human airway epithelial cells

Agnieszka Swiatecka-Urban, Andrea Brown, Sophie Moreau-Marquis, Janhavi Renuka, Bonita Coutermarsh, Roxanna Barnaby, Katherine H. Karlson, Terence R. Flotte, Mitsunori Fukuda, George M Langford, Bruce A. Stanton

Research output: Contribution to journalArticle

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Abstract

The most common mutation in the cystic fibrosis transmembrane conductance regulator (CFTR) gene in individuals with cystic fibrosis, ΔF508, causes retention of ΔF508-CFTR in the endoplasmic reticulum and leads to the absence of CFTR Cl- channels in the apical plasma membrane. Rescue of ΔF508-CFTR by reduced temperature or chemical means reveals that the ΔF508 mutation reduces the half-life of ΔF508-CFTR in the apical plasma membrane. Because ΔF508-CFTR retains some Cl- channel activity, increased expression of ΔF508-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 ΔF508-CFTR in polarized human airway epithelial cells. Accordingly, the goal of this study was to determine the cellular defects in the trafficking of rescued ΔF508-CFTR that lead to the decreased apical membrane half-life of ΔF508-CFTR in polarized human airway epithelial cells. We report that in polarized human airway epithelial cells (CFBE41o-) the ΔF508 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.

Original languageEnglish (US)
Pages (from-to)36762-36772
Number of pages11
JournalJournal of Biological Chemistry
Volume280
Issue number44
DOIs
StatePublished - Nov 4 2005
Externally publishedYes

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ASJC Scopus subject areas

  • Biochemistry

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