Annexin A5 increases the cell surface expression and the chloride channel function of the ΔF508-cystic fibrosis transmembrane regulator

Cystic fibrosis (CF) is caused by a mutation in the cystic fibrosis transmembrane conductance regulator (CFTR) gene. In CF, the most common mutant ΔF508-CFTR is misfolded, is retained in the ER and is rapidly degraded. If conditions could allow ΔF508-CFTR to reach and to stabilize in the plasma membrane, it could partially correct the CF defect. We have previously shown that annexin V (anxA5) binds to both the normal CFTR and the ΔF508-CFTR in a Ca2+-dependent manner and that it regulates the chloride channel function of Wt-CFTR through its membrane integration. Our aim was to extend this finding to the ΔF508-CFTR. Because some studies show that thapsigargin (Tg) increases the ΔF508-CFTR apical expression and induces an increased [Ca2+]i and because anxA5 relocates and binds to the plasma membrane in the presence of Ca2+, we hypothesized that the Tg effect upon ΔF508-CFTR function could involve anxA5. Our results show that raised anxA5 expression induces an augmented function of ΔF508-CFTR due to its increased membrane localization. Furthermore, we show that the Tg effect involves anxA5. Therefore, we suggest that anxA5 is a potential therapeutic target in CF.