Format

Send to

Choose Destination
See comment in PubMed Commons below
J Biol Chem. 2009 Oct 16;284(42):28698-703. doi: 10.1074/jbc.M109.012120. Epub 2009 Aug 13.

Loss of TMEM16A causes a defect in epithelial Ca2+-dependent chloride transport.

Author information

1
Institut für Physiologie, Universität Regensburg, Universitätsstrasse 31, D-93053 Regensburg, Germany.

Abstract

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 Sjöegren syndrome.

PMID:
19679661
PMCID:
PMC2781414
DOI:
10.1074/jbc.M109.012120
[Indexed for MEDLINE]
Free PMC Article
PubMed Commons home

PubMed Commons

0 comments
How to join PubMed Commons

    Supplemental Content

    Full text links

    Icon for HighWire Icon for PubMed Central
    Loading ...
    Support Center