Tian, Yuemin and Kongsuphol, Patthara and Hug, Martin and Ousingsawat, Jiraporn and Witzgall, Ralph and Schreiber, Rainer and Kunzelmann, Karl (2011) Calmodulin-dependent activation of the epithelial calcium-dependent chloride channel TMEM16A. FASEB JOURNAL, 25 (3). pp. 1058-1068. ISSN 0892-6638, 1530-6860
Full text not available from this repository. (Request a copy)Abstract
TMEM16A (anoctamin 1, Ano1), a member of a family of 10 homologous proteins, has been shown to form an essential component of Ca2+ -activated Cl- channels. TMEM16A-null mice exhibit severe defects in epithelial transport along with tracheomalacia and death within 1 mo after birth. Despite its outstanding physiological significance, the mechanisms for activation of TMEM16A remain obscure. TMEM16A is activated on increase in intracellular Ca2+, but it is unclear whether Ca2+ binds directly to the channel or whether additional components are required. We demonstrate that TMEM16A is strictly membrane localized and requires cytoskeletal interactions to be fully activated. Despite the need for cytosolic ATP for full activation, phosphorylation by protein kinases is not required. In contrast, the Ca2+ binding protein calmodulin appears indispensable and interacts physically with TMEM16A. Openers of small-and intermediate-conductance Ca2+ -activated potassium channels known to interact with calmodulin, such as 1-EBIO, DCEBIO, or riluzole, also activated TMEM16A. These results reinforce the use of these compounds for activation of electrolyte secretion in diseases such as cystic fibrosis.-Tian, Y., Kongsuphol, P., Hug, M., Ousingsawat, J., Witzgall, R., Schreiber, R., Kunzelmann, K. Calmodulin-dependent activation of the epithelial calcium-dependent chloride channel TMEM16A. FASEB J. 25, 1058-1068 (2011). www.fasebj.org
| Item Type: | Article |
|---|---|
| Uncontrolled Keywords: | CA2+-ACTIVATED K+ CHANNELS; STIMULATES CL-SECRETION; SMOOTH-MUSCLE-CELLS; INTERMEDIATE-CONDUCTANCE; PROTEIN-KINASE; INTERSTITIAL-CELLS; POTASSIUM CHANNELS; CYSTIC-FIBROSIS; MOUSE JEJUNUM; ACINAR-CELLS; Ca2+ -activated Cl- channels; anoctamin 1; exocytosis; SK4; 1-EBIO; cystic fibrosis |
| Subjects: | 500 Science > 570 Life sciences |
| Divisions: | Biology, Preclinical Medicine > Institut für Physiologie > Prof. Dr. Karl Kunzelmann Biology, Preclinical Medicine > Institut für Anatomie > Lehrstuhl für Molekulare und zelluläre Anatomie > Prof. Dr. Ralph Witzgall |
| Depositing User: | Dr. Gernot Deinzer |
| Date Deposited: | 25 Jun 2020 08:38 |
| Last Modified: | 25 Jun 2020 08:38 |
| URI: | https://pred.uni-regensburg.de/id/eprint/21240 |
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