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Is CFTR-delF508 Really Absent from the Apical Membrane of the Airway Epithelium?

Lookup NU author(s): Dr Lee Borthwick, Phil Botha, Dr Malcolm Brodlie, Aaron Gardner, Dr David Bourn, Dr Michael Gray, Professor Andrew FisherORCiD



Background: Understanding where mutant CFTR is localised in airway epithelia is essential in guiding the best therapeutic approach to correct the dysfunction of the CFTR protein. The widely held paradigm is that CF patients harbouring the commonest mutation, CFTR-delF508, trap CFTR within the endoplasmic reticulum and target it for degradation. However there are conflicting reports concerning expression and localisation of CFTR-delF508 in lung tissue. To attempt to resolve this fundamental issue we developed a novel approach to measure CFTR-delF508 in the lower airways of patients who have undergone lung transplantation for advanced CF. By sampling CF and non-CF epithelium simultaneously from the same individual, confounding factors of different airway microenvironments which may have influenced previous observations can be overcome. Methods: Epithelia sampled by bronchial brushing above (CF) and below (non-CF) the bronchial anastomosis were stained for CFTR and the localisation and level of expression assessed (n = 12). Results: There was no significant difference in the proportion of tall columnar cells showing CFTR immunostaining as a discrete band at the apical membrane in cells harbouring the CFTR-delF508 mutation compared to non-CF cells (p = 0.21, n = 12). However, the amount of CFTR expressed at the apical surface was reduced by similar to 50% in CF cells compared to non-CF cells (p = 0.04, n = 5). Conclusions: Our novel observation challenges the prevailing paradigm that CFTR is essentially absent from the apical membrane of respiratory cells harbouring the CFTR-delF508 mutation. Moreover, it raises the possibility that the new generation of CFTR potentiators may offer a realistic therapeutic option for CF patients.

Publication metadata

Author(s): Borthwick LA, Botha P, Verdon B, Brodlie MJ, Gardner A, Bourn D, Johnson GE, Gray MA, Fisher AJ

Publication type: Article

Publication status: Published

Journal: PLoS One

Year: 2011

Volume: 6

Issue: 8

Print publication date: 01/08/2011

ISSN (electronic): 1932-6203

Publisher: Public Library of Science


DOI: 10.1371/journal.pone.0023226


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Funder referenceFunder name
PJ540Cystic Fibrosis Trust UK