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Expression cloning of TMEM16A as a calcium-activated chloride channel subunit

Item Type:Article
Title:Expression cloning of TMEM16A as a calcium-activated chloride channel subunit
Creators Name:Schroeder, B.C. and Cheng, T. and Jan, Y.N. and Jan, L.Y.
Abstract:Calcium-activated chloride channels (CaCCs) are major regulators of sensory transduction, epithelial secretion, and smooth muscle contraction. Other crucial roles of CaCCs include action potential generation in Characean algae and prevention of polyspermia in frog egg membrane. None of the known molecular candidates share properties characteristic of most CaCCs in native cells. Using Axolotl oocytes as an expression system, we have identified TMEM16A as the Xenopus oocyte CaCC. The TMEM16 family of "transmembrane proteins with unknown function" is conserved among eukaryotes, with family members linked to tracheomalacia (mouse TMEM16A), gnathodiaphyseal dysplasia (human TMEM16E), aberrant X segregation (a Drosophila TMEM16 family member), and increased sodium tolerance (yeast TMEM16). Moreover, mouse TMEM16A and TMEM16B yield CaCCs in Axolotl oocytes and mammalian HEK293 cells and recapitulate the broad CaCC expression. The identification of this new family of ion channels may help the development of CaCC modulators for treating diseases including hypertension and cystic fibrosis.
Keywords:Ambystoma, Cell Line, Chloride Channels, Molecular Cloning, Molecular Sequence Data, Oocytes, Xenopus Proteins, Animals, Mice, Xenopus Laevis
Publisher:Cell Press
Page Range:1019-1029
Date:19 September 2008
Official Publication:https://doi.org/10.1016/j.cell.2008.09.003
PubMed:View item in PubMed

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