| First Author | Ousingsawat J | Year | 2009 |
| Journal | J Biol Chem | Volume | 284 |
| Issue | 42 | Pages | 28698-703 |
| PubMed ID | 19679661 | Mgi Jnum | J:156349 |
| Mgi Id | MGI:4420365 | Doi | 10.1074/jbc.M109.012120 |
| Citation | Ousingsawat J, et al. (2009) Loss of TMEM16A causes a defect in epithelial Ca2+-dependent chloride transport. J Biol Chem 284(42):28698-703 |
| abstractText | Molecular identification of the Ca(2+)-dependent chloride channel TMEM16A (ANO1) provided a fundamental step in understanding Ca(2+)-dependent Cl(-) secretion in epithelia. TMEM16A is an intrinsic constituent of Ca(2+)-dependent Cl(-) channels in cultured epithelia and may control salivary output, but its physiological role in native epithelial tissues remains largely obscure. Here, we demonstrate that Cl(-) secretion in native epithelia activated by Ca(2+)-dependent agonists is missing in mice lacking expression of TMEM16A. Ca(2+)-dependent Cl(-) transport was missing or largely reduced in isolated tracheal and colonic epithelia, as well as hepatocytes and acinar cells from pancreatic and submandibular glands of TMEM16A(-/-) animals. Measurement of particle transport on the surface of tracheas ex vivo indicated largely reduced mucociliary clearance in TMEM16A(-/-) mice. These results clearly demonstrate the broad physiological role of TMEM16A(-/-) for Ca(2+)-dependent Cl(-) secretion and provide the basis for novel treatments in cystic fibrosis, infectious diarrhea, and Sjoegren syndrome. |
