Schreiber, Rainer and Faria, Diana and Skryabin, Boris V. and Wanitchakool, Podchanart and Rock, Jason R. and Kunzelmann, Karl (2015) Anoctamins support calcium-dependent chloride secretion by facilitating calcium signaling in adult mouse intestine. PFLUGERS ARCHIV-EUROPEAN JOURNAL OF PHYSIOLOGY, 467 (6). pp. 1203-1213. ISSN 0031-6768, 1432-2013
Full text not available from this repository. (Request a copy)Abstract
Intestinal epithelial electrolyte secretion is activated by increase in intracellular cAMP or Ca2+ and opening of apical Cl- channels. In infants and young animals, but not in adults, Ca2+-activated chloride channels may cause secretory diarrhea during rotavirus infection. While detailed knowledge exists concerning the contribution of cAMP-activated cystic fibrosis transmembrane conductance regulator (CFTR) channels, analysis of the role of Ca2+-dependent Cl- channels became possible through identification of the anoctamin (TMEM16) family of proteins. We demonstrate expression of several anoctamin paralogues in mouse small and large intestines. Using intestinal-specific mouse knockout models for anoctamin 1 (Ano1) and anoctamin 10 (Ano10) and a conventional knockout model for anoctamin 6 (Ano6), we demonstrate the role of anoctamins for Ca2+-dependent Cl- secretion induced by the muscarinic agonist carbachol (CCH). Ano1 is preferentially expressed in the ileum and large intestine, where it supports Ca2+-activated Cl- secretion. In contrast, Ano10 is essential for Ca2+-dependent Cl- secretion in jejunum, where expression of Ano1 was not detected. Although broadly expressed, Ano6 has no role in intestinal cholinergic Cl- secretion. Ano1 is located in a basolateral compartment/membrane rather than in the apical membrane, where it supports CCH-induced Ca2+ increase, while the essential and possibly only apical Cl- channel is CFTR. These results define a new role of Ano1 for intestinal Ca2+-dependent Cl- secretion and demonstrate for the first time a contribution of Ano10 to intestinal transport.
| Item Type: | Article |
|---|---|
| Uncontrolled Keywords: | CFTR; CHANNEL; ACTIVATION; TMEM16A; PROTEIN; COLON; CAMP; CA2+; EXPRESSION; TRANSPORT; TMEM16A; TMEM16F; TMEM16K; Anoctamin 1; Anoctamin 6; Anoctamin 10; Ano1; Ano6; Ano10; Ca2+-activated Cl- channels; Colon; Small intestine; Ileum; Jejunumchloride secretion |
| Subjects: | 500 Science > 570 Life sciences |
| Divisions: | Biology, Preclinical Medicine > Institut für Physiologie > Prof. Dr. Karl Kunzelmann |
| Depositing User: | Dr. Gernot Deinzer |
| Date Deposited: | 15 Jul 2019 13:51 |
| Last Modified: | 15 Jul 2019 13:51 |
| URI: | https://pred.uni-regensburg.de/id/eprint/5445 |
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