NHE-RF1 protein rescues ΔF508-CFTR function

Florian Bossard, Amal Robay, Gilles Toumaniantz, Shehrazade Dahimene, Frédéric Becq, Jean Merot, Chantal Gauthier

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In cystic fibrosis (CF), the ΔF508-CFTR anterograde trafficking from the endoplasmic reticulum to the plasma membrane is inefficient. New strategies for increasing the delivery of ΔF508-CFTR to the apical membranes are thus pathophysiologically relevant targets to study for CF treatment. Recent studies have demonstrated that PDZ-containing proteins play an essential role in determining polarized plasma membrane expression of ionic transporters. In the present study we have hypothesized that the PDZ-containing protein NHE-RF1, which binds to the carboxy terminus of CFTR, rescues ΔF508-CFTR expression in the apical membrane of epithelial cells. The plasmids encoding ΔF508-CFTR and NHE-RF1 were intranuclearly injected in A549 or Madin-Darby canine kidney (MDCK) cells, and ΔF508-CFTR channel activity was functionally assayed using SPQ fluorescent probe. Cells injected with ΔF508-CFTR alone presented a low chloride channel activity, whereas its coexpression with NHE-RF1 significantly increased both the basal and forskolin-activated chloride conductances. This last effect was lost with ΔF508-CFTR deleted of its 13 last amino acids or by injection of a specific NHE-RF1 antisense oligonucleotide, but not by NHE-RF1 sense oligonucleotide. Immunocytochemical analysis performed in MDCK cells transiently transfected with ΔF508-CFTR further revealed that NHE-RF1 specifically determined the apical plasma membrane expression of ΔF508-CFTR but not that of a trafficking defective mutant potassium channel (KCNQ1). These data demonstrate that the modulation of the expression level of CFTR protein partners, like NHE-RF1, can rescue ΔF508-CFTR activity.

Original languageEnglish
Pages (from-to)L1085-L1094
JournalAmerican Journal of Physiology - Lung Cellular and Molecular Physiology
Issue number5
Publication statusPublished - May 2007



  • Cystic fibrosis
  • Na/H exchanger regulatory factor isoform 1
  • Polarized expression
  • Traffic
  • ΔF508 cystic fibrosis transmembrane conductance regulator

ASJC Scopus subject areas

  • Physiology
  • Pulmonary and Respiratory Medicine
  • Physiology (medical)
  • Cell Biology

Cite this

Bossard, F., Robay, A., Toumaniantz, G., Dahimene, S., Becq, F., Merot, J., & Gauthier, C. (2007). NHE-RF1 protein rescues ΔF508-CFTR function. American Journal of Physiology - Lung Cellular and Molecular Physiology, 292(5), L1085-L1094. https://doi.org/10.1152/ajplung.00445.2005