Benedetto, Roberta and Ousingsawat, Jiraporn and Wanitchakool, Podchanart and Zhang, Yong and Holtzman, Michael J. and Amaral, Margarida and Rock, Jason R. and Schreiber, Rainer and Kunzelmann, Karl (2017) Epithelial Chloride Transport by CFTR Requires TMEM16A. SCIENTIFIC REPORTS, 7: 12397. ISSN 2045-2322,
Full text not available from this repository. (Request a copy)Abstract
Cystic Fibrosis Transmembrane Conductance Regulator (CFTR) is the secretory chloride/bicarbonate channel in airways and intestine that is activated through ATP binding and phosphorylation by protein kinase A, but fails to operate in cystic fibrosis (CF). TMEM16A (also known as anoctamin 1, ANO1) is thought to function as the Ca2+ activated secretory chloride channel independent of CFTR. Here we report that tissue specific knockout of the TMEM16A gene in mouse intestine and airways not only eliminates Ca2+-activated Cl-currents, but unexpectedly also abrogates CFTR-mediated Cl-secretion and completely abolishes cAMP-activated whole cell currents. The data demonstrate fundamentally new roles of TMEM16A in differentiated epithelial cells: TMEM16A provides a mechanism for enhanced ER Ca2+ store release, possibly engaging Store Operated cAMP Signaling (SOcAMPS) and activating Ca2+ regulated adenylyl cyclases. TMEM16A is shown to be essential for proper activation and membrane expression of CFTR. This intimate regulatory relationship is the cause for the functional overlap of CFTR and Ca2+-dependent chloride transport.
| Item Type: | Article |
|---|---|
| Uncontrolled Keywords: | TRANSMEMBRANE CONDUCTANCE REGULATOR; CYSTIC-FIBROSIS; FLUID SECRETION; HCO3-SECRETION; MOUSE AIRWAYS; CA2+ SIGNALS; CHANNEL; CAMP; CELLS; ACTIVATION; |
| Subjects: | 500 Science > 570 Life sciences |
| Divisions: | Biology, Preclinical Medicine > Institut für Physiologie > Prof. Dr. Karl Kunzelmann |
| Depositing User: | Dr. Gernot Deinzer |
| Date Deposited: | 14 Dec 2018 13:20 |
| Last Modified: | 25 Feb 2019 15:26 |
| URI: | https://pred.uni-regensburg.de/id/eprint/2154 |
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