A truncated CFTR protein rescues endogenous ΔF508-CFTR and corrects chloride transport in mice

Estelle Cormet-Boyaka, Jeong S. Hong, Bakhram K. Berdiev, James A. Fortenberry, Jessica Rennolds, J. P. Clancy, Dale J. Benos, Prosper N. Boyaka, Eric J. Sorscher

Research output: Contribution to journalArticle

11 Citations (Scopus)

Abstract

Cystic fibrosis (CF) is most frequently associated with deletion of phenylalanine at position 508 (ΔF508) in the CF transmembrane conductance regulator (CFTR) protein. The ΔF508-CFTR mutant protein exhibits a folding defect that affects its processing and impairs chloride-channel function. This study aimed to determine whether CFTR fragments approximately half the size of wild-type CFTR and complementary to the portion of CFTR bearing the mutation can specifically rescue the processing of endogenous ΔF508-CFTR in vivo. cDNA encoding CFTR fragments were delivered to human airway epithelial cells and mice harboring endogenous ΔF508-CFTR. Delivery of small CFTR fragments, which do not act as chloride channels by themselves, rescue ΔF508-CFTR. Therefore, we can speculate that the presence of the CFTR fragment, which does not harbor a mutation, might facilitate intermolecular interactions. The rescue of CFTR was evident by the restoration of chloride transport in human CFBE41o- bronchial epithelial cells expressing ΔF508-CFTR in vitro. More important, nasal administration of an adenovirus expressing a complementary CFTR fragment restored some degree of CFTR activity in the nasal airways of ΔF508 homozygous mice in vivo. These findings identify complementary protein fragments as a viable in vivo approach for correcting disease-causing misfolding of plasma membrane proteins.

Original languageEnglish
Pages (from-to)3743-3751
Number of pages9
JournalFASEB Journal
Volume23
Issue number11
DOIs
Publication statusPublished - 2009
Externally publishedYes

Fingerprint

Chloride Channels
Chlorides
Bearings (structural)
Epithelial Cells
Intranasal Administration
Cystic Fibrosis Transmembrane Conductance Regulator
Mutation
Mutant Proteins
Cell membranes
Ports and harbors
Processing
Phenylalanine
Nose
Adenoviridae
Cystic Fibrosis
Restoration
Blood Proteins
Membrane Proteins
Proteins
Complementary DNA

Keywords

  • Cystic fibrosis
  • In vivo rescue
  • Processing
  • Transcomplementation

ASJC Scopus subject areas

  • Biochemistry
  • Biotechnology
  • Genetics
  • Molecular Biology

Cite this

Cormet-Boyaka, E., Hong, J. S., Berdiev, B. K., Fortenberry, J. A., Rennolds, J., Clancy, J. P., ... Sorscher, E. J. (2009). A truncated CFTR protein rescues endogenous ΔF508-CFTR and corrects chloride transport in mice. FASEB Journal, 23(11), 3743-3751. https://doi.org/10.1096/fj.08-127878

A truncated CFTR protein rescues endogenous ΔF508-CFTR and corrects chloride transport in mice. / Cormet-Boyaka, Estelle; Hong, Jeong S.; Berdiev, Bakhram K.; Fortenberry, James A.; Rennolds, Jessica; Clancy, J. P.; Benos, Dale J.; Boyaka, Prosper N.; Sorscher, Eric J.

In: FASEB Journal, Vol. 23, No. 11, 2009, p. 3743-3751.

Research output: Contribution to journalArticle

Cormet-Boyaka, E, Hong, JS, Berdiev, BK, Fortenberry, JA, Rennolds, J, Clancy, JP, Benos, DJ, Boyaka, PN & Sorscher, EJ 2009, 'A truncated CFTR protein rescues endogenous ΔF508-CFTR and corrects chloride transport in mice', FASEB Journal, vol. 23, no. 11, pp. 3743-3751. https://doi.org/10.1096/fj.08-127878
Cormet-Boyaka E, Hong JS, Berdiev BK, Fortenberry JA, Rennolds J, Clancy JP et al. A truncated CFTR protein rescues endogenous ΔF508-CFTR and corrects chloride transport in mice. FASEB Journal. 2009;23(11):3743-3751. https://doi.org/10.1096/fj.08-127878
Cormet-Boyaka, Estelle ; Hong, Jeong S. ; Berdiev, Bakhram K. ; Fortenberry, James A. ; Rennolds, Jessica ; Clancy, J. P. ; Benos, Dale J. ; Boyaka, Prosper N. ; Sorscher, Eric J. / A truncated CFTR protein rescues endogenous ΔF508-CFTR and corrects chloride transport in mice. In: FASEB Journal. 2009 ; Vol. 23, No. 11. pp. 3743-3751.
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