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SERCA and PMCA pumps contribute to the deregulation of Ca2+ homeostasis in human CF epithelial cells |
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Published in | Biochimica et biophysica acta. 2015, vol. 1853, no. 5, p. 892-903 | |
Abstract | Cystic Fibrosis (CF) disease is caused by mutations in the CFTR gene (CF transmembrane conductance regulator). F508 deletion is the most represented mutation, and F508del-CFTR is absent of plasma membrane and accumulates into the endoplasmic reticulum (ER) compartment. Using specific Ca(2+) genetics cameleon probes, we showed in the human bronchial CF epithelial cell line CFBE that ER Ca(2+) concentration was strongly increased compared to non-CF (16HBE) cells, and normalized by the F508del-CFTR corrector agent, VX-809. We also showed that ER F508del-CFTR retention increases SERCA (Sarcoplasmic/Reticulum Ca(2+) ATPase) pump activity whereas PMCA (Plasma Membrane Ca(2+) ATPase) activities were reduced in these CF cells compared to corrected CF cells (VX-809) and non-CF cells. We are showing for the first time CFTR/SERCA and CFTR/PMCA interactions that are modulated in CF cells and could explain part of Ca(2+) homeostasis deregulation due to mislocalization of F508del-CFTR. Using ER or mitochondria genetics Ca(2+) probes, we are showing that ER Ca(2+) content, mitochondrial Ca(2+) uptake, SERCA and PMCA pump, activities are strongly affected by the localization of F508del-CFTR protein. | |
Identifiers | PMID: 25661196 | |
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Research groups | Culture Primaire de myoblastes humains (208) Signaux intracellulaires (210) | |
Citation (ISO format) | PHILIPPE, Réginald et al. SERCA and PMCA pumps contribute to the deregulation of Ca2+ homeostasis in human CF epithelial cells. In: Biochimica et biophysica acta, 2015, vol. 1853, n° 5, p. 892-903. doi: 10.1016/j.bbamcr.2015.01.010 https://archive-ouverte.unige.ch/unige:75584 |