Cystic fibrosis transmembrane conductance regulator (CFTR) functionality is dependent on coatomer protein I (COPI)

Ying Yu, Oleksandr Platoshyn, Olga Safrina, Igor Tsigelny, Jason X.J. Yuan, Steven H. Keller

Research output: Contribution to journalArticlepeer-review

5 Scopus citations


Background Information. Cystic fibrosis results from mutations in the ABC transporter CFTR (cystic fibrosis trans-membrane conductance regulator), which functions as a cAMP-regulated anion channel. The most prevalent mutation in CFTR, the Phe508 deletion, results in the generation of a trafficking and functionally deficient channel. The cellular machineries involved in modulating CFTR trafficking and function have not been fully characterized. In the present study, we identified a role for the COPI (coatomer protein I) cellular trafficking machinery in the development of the CFTR polypeptide into a functional chloride channel. To examine the role of COPI in CFTR biosynthesis, we employed the cell line IdIF, which harbours a temperature-sensitive mutation in ε-COP, a COPI subunit, to inhibit COPI function and then determined whether the CFTR polypeptide produced from the transfected gene developed into a cAMP-regulated chloride channel. Results. When COPI was inactivated in the IdIF cells by an elevated temperature pulse (39°C), the CFTR polypeptide was detected on the cell surface by immunofluorescence microscopy and cell-surface biotinylation. Therefore, CFTR proceeded upstream in the secretory pathway in the absence of COPI function, a result demonstrated previously by others. In contrast, electrophysiological measurements indicated an absence of cAMP-stimulated chloride efflux, suggesting that channel function was impaired. In comparison, expression of CFTR at the same elevated temperature (39°C) in an ε-COP-rescued cell line [IdIF(IdIF)], which has an introduced wild-type ε-COP gene in addition to the mutant ε-COP gene, showed restoration of cAMP-stimulated channel activity, confirming the requirement of COPI for channel function. Conclusions. These results therefore suggest that generation of the folded-functional conformation of CFTR requires COPI.

Original languageEnglish (US)
Pages (from-to)433-444
Number of pages12
JournalBiology of the Cell
Issue number8
StatePublished - Aug 2007
Externally publishedYes


  • Coatomer protein
  • Cystic fibrosis
  • Endoplasmic reticulum
  • IdIF cell
  • Ion-channel trafficking

ASJC Scopus subject areas

  • Cell Biology


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