Martins, Joana Raquel and Kongsuphol, Patthara and Sammels, Eva and Dahimene, Shehrazade and AlDehni, Fadi and Clarke, Luka Alexander and Schreiber, Rainer and de Smedt, Humbert and Amaral, Margarida D. and Kunzelmann, Karl (2011) F508del-CFTR increases intracellular Ca2+ signaling that causes enhanced calcium-dependent Cl- conductance in cystic fibrosis. BIOCHIMICA ET BIOPHYSICA ACTA-MOLECULAR BASIS OF DISEASE, 1812 (11). pp. 1385-1392. ISSN 0925-4439, 1879-260X
Full text not available from this repository. (Request a copy)Abstract
In many cells, increase in intracellular calcium ([Ca2+](i)) activates a Ca2+-dependent chloride (Cl-) conductance (CaCC). CaCC is enhanced in cystic fibrosis (CF) epithelial cells lacking Cl- transport by the CF transmembrane conductance regulator (CFTR). Here, we show that in freshly isolated nasal epithelial cells of F508del-homozygous CF patients, expression of TMEM16A and bestrophin 1 was unchanged. However, calcium signaling was strongly enhanced after induction of expression of F508del-CF1'R, which is unable to exit the endoplasmic reticulum (ER). Since receptor-mediated [Ca2+](i) increase is Cl- dependent, we suggested that F508del-CFTR may function as an ER chloride counter-ion channel for Ca2+. This was confirmed by expression of the double mutant F508del/G551D-CFTR, which remained in the ER but had no effects on [Ca2+];. Moreover, F508del-CFTR could serve as a scavenger for inositol-1,4,5-trisphosphate [IP3] receptor binding protein released with IP3 (IRBIT). Our data may explain how ER-localized F508del-CFTR controls intracellular Ca2+ signaling. (C) 2011 Elsevier B.V. All rights reserved.
| Item Type: | Article |
|---|---|
| Uncontrolled Keywords: | SARCOPLASMIC-RETICULUM; ENDOPLASMIC-RETICULUM; BRONCHIAL EPITHELIUM; CHLORIDE CHANNELS; PROTEIN; CFTR; ACTIVATION; SECRETION; REGULATOR; RECEPTOR; TMEM16A; Bestrophin 1; Ca2+ activated Cl- current; CF inflammation; Purinergic receptor; Cl- channel |
| Subjects: | 500 Science > 570 Life sciences |
| Divisions: | Biology, Preclinical Medicine > Institut für Physiologie > Prof. Dr. Karl Kunzelmann |
| Depositing User: | Dr. Gernot Deinzer |
| Date Deposited: | 27 May 2020 08:14 |
| Last Modified: | 27 May 2020 08:14 |
| URI: | https://pred.uni-regensburg.de/id/eprint/19866 |
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