SERCA and PMCA pumps contribute to the deregulation of Ca<sup>2+</sup> homeostasis in human CF epithelial cells

Philippe, Réginald; Antigny, Fabrice; Buscaglia, Paul; Norez, Caroline; Becq, Frédéric; Frieden, Maud; Mignen, Olivier

doi:10.1016/j.bbamcr.2015.01.010

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Title		SERCA and PMCA pumps contribute to the deregulation of Ca²⁺ homeostasis in human CF epithelial cells
Authors		Philippe, Réginald Antigny, Fabrice Buscaglia, Paul Norez, Caroline Becq, Frédéric Frieden, Maud Mignen, Olivier
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		DOI: 10.1016/j.bbamcr.2015.01.010 PMID: 25661196
Full text		Article (Published version) (1.1 MB) - Limited access to UNIGE
Structures		Faculté de médecine / Section de médecine fondamentale / Département de physiologie cellulaire et métabolisme
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