Kongsuphol, Patthara and Schreiber, Rainer and Kraidith, Kamonshanok and Kunzelmann, Karl (2011) CFTR induces extracellular acid sensing in Xenopus oocytes which activates endogenous Ca2+-activated Cl- conductance. PFLUGERS ARCHIV-EUROPEAN JOURNAL OF PHYSIOLOGY, 462 (3). pp. 479-487. ISSN 0031-6768, 1432-2013
Full text not available from this repository. (Request a copy)Abstract
The cystic fibrosis transmembrane conductance regulator (CFTR) produces a cyclic adenosine monophosphate (cAMP)-dependent Cl- conductance of distinct properties that is essential for electrolyte secretion in human epithelial tissues. However, the functional consequences of CFTR expression are multifaceted, encompassing much more than simply supplying a cellular cAMP-regulated Cl- conductance. When we expressed CFTR in Xenopus oocytes, we found that extracellular acidic pH activates a Ca2+-dependent outwardly rectifying Cl- conductance that does not reflect CFTR activity. The proton-activated Cl- conductance showed biophysical and pharmacological features of a Ca2+-dependent Cl- conductance, most likely mediated by Xenopus TMEM16A. In contrast to the effects of extracellular acidification, intracellular acidification did not activate an endogenous Cl- conductance. Proton/CFTR-mediated activation of human TMEM16A was also detected in HEK293 cells. The gating mutant G551D-CFTR conferred proton sensitivity, while deltaF508-CFTR enabled proton activation of TMEM16A only in Xenopus oocytes, which, unlike HEK293 cells, allow deltaF508-CFTR to be trafficked to the cell membrane. Activation of TMEM16A by lysophosphatidic acid was enhanced in the presence of CFTR but was additive with activation by extracellular protons. Because expression of CFTR-E1474X did not confer proton sensitivity, we propose that CFTR translocates a proton receptor to the plasma membrane via its PDZ-binding domain.
| Item Type: | Article |
|---|---|
| Uncontrolled Keywords: | FIBROSIS AIRWAY EPITHELIA; CYSTIC-FIBROSIS; CHLORIDE CHANNEL; LYSOPHOSPHATIDIC ACID; CALCIUM; INHIBITION; OSTEOPENIA; REGULATOR; SECRETION; TMEM16A; Cystic fibrosis transmembrane conductance regulator; CFTR; Acid; Protons; Delta F508-CFTR; Ca2+-activated chloride secretion; CaCC; TMEM16A |
| Subjects: | 500 Science > 570 Life sciences |
| Divisions: | Biology, Preclinical Medicine > Institut für Physiologie > Prof. Dr. Karl Kunzelmann |
| Depositing User: | Dr. Gernot Deinzer |
| Date Deposited: | 02 Jun 2020 07:51 |
| Last Modified: | 02 Jun 2020 07:51 |
| URI: | https://pred.uni-regensburg.de/id/eprint/20359 |
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