Calcium homeostasis is abnormal in cystic fibrosis airway epithelial cells but is normalized after rescue of F508del-CFTR

Fabrice Antigny (1) , Caroline Norez (1) , Frédéric Becq (1) , Clarisse Vandebrouck (1)

1 IPBC - Institut de physiologie et biologie cellulaires

Retention of F508del-CFTR proteins in the endoplasmic reticulum (ER) is dependent upon chaperone proteins, many of which require Ca2+ for optimal activity. Here, we show in human tracheal gland CF-KM4 cells, that after correction of F508del-CFTR trafficking by miglustat (Nbutyldeoxynojirimycin) or low temperature (27 ◦C), the Ca2+ mobilization is decreased compared to uncorrected cells and becomes identical to the Ca2+ response observed in non-CF MM39 cells. In CF-KM4 and human nasal epithelial CF15 cells, we also show that inhibiting vesicular trafficking by nocodazole prevents not only the rescue of F508del-CFTR but also the Ca2+ mobilization decrease. Finally, experiments using the CFTR inhibitor CFTRinh-172 showed that the presence but not the channel activity of F508del-CFTR at the plasma membrane is required to decrease the Ca2+ mobilization in corrected CF cells. These findings show that correction of the abnormal trafficking of F508del-CFTR proteins might have profound consequences on cellular homeostasis such as the control of intracellular Ca2+ level.

Mots clés: Cystic fibrosis; Calcium signalling; Pharmacology; F508del-CFTR; Trafficking; Miglustat; Cystic fibrosis

Domaines: Biologie cellulaire; Physiologie [q-bio.TO]; Pneumologie et système respiratoire; Pharmacologie

Fabrice Antigny, Caroline Norez, Frédéric Becq, Clarisse Vandebrouck. Calcium homeostasis is abnormal in cystic fibrosis airway epithelial cells but is normalized after rescue of F508del-CFTR. Cell Calcium, 2007, 43 (2), pp.175-183. ⟨10.1016/j.ceca.2007.05.002⟩. ⟨hal-00389764⟩