SERCA and PMCA pumps contribute to the deregulation of Ca2+ homeostasis in human CF epithelial cells
Copyright policy )SERCA and PMCA pumps contribute to the deregulation of Ca2+ homeostasis in human CF epithelial cells
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 Ca2+ genetics cameleon probes, we showed in the human bronchial CF epithelial cell line CFBE that ER Ca2+ 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 Ca2+ ATPase) pump activity whereas PMCA (Plasma Membrane Ca2+ 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 Ca2+ homeostasis deregulation due to mislocalization of F508del-CFTR. Using ER or mitochondria genetics Ca2+ probes, we are showing that ER Ca2+ content, mitochondrial Ca2+ uptake, SERCA and PMCA pump, activities are strongly affected by the localization of F508del-CFTR protein.
- French National Centre for Scientific Research France
- University of Geneva Switzerland
- University of Nantes France
- UNIVERSITE BRETAGNE OCCIDENTALE France
- Centre Hospitalier Régional Universitaire de Brest France
MESH: Cystic Fibrosis / pathology*, Cystic Fibrosis, [SDV]Life Sciences [q-bio], MESH: Calcium / metabolism*, Aminopyridines, Cystic Fibrosis Transmembrane Conductance Regulator, [SDV.BC.IC] Life Sciences [q-bio]/Cellular Biology/Cell Behavior [q-bio.CB], MESH: Epithelial Cells / drug effects, Endoplasmic Reticulum, MESH: Benzodioxoles / pharmacology, Adenosine Triphosphate, PMCA, [SDV.BC.IC]Life Sciences [q-bio]/Cellular Biology/Cell Behavior [q-bio.CB], Homeostasis, MESH: Cystic Fibrosis Transmembrane Conductance Regulator, MESH: Endoplasmic Reticulum / metabolism, MESH: Adenosine Triphosphate / pharmacology, MESH: Plasma Membrane Calcium-Transporting ATPases / metabolism*, Mitochondria, MESH: Homeostasis* / drug effects, MESH: Protein Binding / drug effects, Protein Binding, MESH: Aminopyridines / pharmacology, MESH: Bronchi / pathology, Bronchi, MESH: Epithelial Cells / enzymology*, [SDV.BC]Life Sciences [q-bio]/Cellular Biology, 612, MESH: Epithelial Cells / pathology, Cystic fibrosis, F508del-CFTR, Cell Line, Sarcoplasmic Reticulum Calcium-Transporting ATPases, MESH: Sarcoplasmic Reticulum Calcium-Transporting ATPases / metabolism*, Plasma Membrane Calcium-Transporting ATPases, SERCA, Humans, Benzodioxoles, [SDV.BC] Life Sciences [q-bio]/Cellular Biology, Molecular Biology, MESH: Humans, MESH: Endoplasmic Reticulum / drug effects, MESH: Mitochondria / drug effects, Calcium signaling, Epithelial Cells, Cell Biology, MESH: Cell Line, MESH: Mitochondria / metabolism, Calcium, ddc: ddc:612
MESH: Cystic Fibrosis / pathology*, Cystic Fibrosis, [SDV]Life Sciences [q-bio], MESH: Calcium / metabolism*, Aminopyridines, Cystic Fibrosis Transmembrane Conductance Regulator, [SDV.BC.IC] Life Sciences [q-bio]/Cellular Biology/Cell Behavior [q-bio.CB], MESH: Epithelial Cells / drug effects, Endoplasmic Reticulum, MESH: Benzodioxoles / pharmacology, Adenosine Triphosphate, PMCA, [SDV.BC.IC]Life Sciences [q-bio]/Cellular Biology/Cell Behavior [q-bio.CB], Homeostasis, MESH: Cystic Fibrosis Transmembrane Conductance Regulator, MESH: Endoplasmic Reticulum / metabolism, MESH: Adenosine Triphosphate / pharmacology, MESH: Plasma Membrane Calcium-Transporting ATPases / metabolism*, Mitochondria, MESH: Homeostasis* / drug effects, MESH: Protein Binding / drug effects, Protein Binding, MESH: Aminopyridines / pharmacology, MESH: Bronchi / pathology, Bronchi, MESH: Epithelial Cells / enzymology*, [SDV.BC]Life Sciences [q-bio]/Cellular Biology, 612, MESH: Epithelial Cells / pathology, Cystic fibrosis, F508del-CFTR, Cell Line, Sarcoplasmic Reticulum Calcium-Transporting ATPases, MESH: Sarcoplasmic Reticulum Calcium-Transporting ATPases / metabolism*, Plasma Membrane Calcium-Transporting ATPases, SERCA, Humans, Benzodioxoles, [SDV.BC] Life Sciences [q-bio]/Cellular Biology, Molecular Biology, MESH: Humans, MESH: Endoplasmic Reticulum / drug effects, MESH: Mitochondria / drug effects, Calcium signaling, Epithelial Cells, Cell Biology, MESH: Cell Line, MESH: Mitochondria / metabolism, Calcium, ddc: ddc:612
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