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

研究成果: Article査読

166 被引用数 (Scopus)

抄録

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.

本文言語English
ページ(範囲)36762-36772
ページ数11
ジャーナルJournal of Biological Chemistry
280
44
DOI
出版ステータスPublished - 2005 11月 4
外部発表はい

ASJC Scopus subject areas

  • 生化学
  • 分子生物学
  • 細胞生物学

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