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

      1 , , ,
      Cell
      Elsevier BV

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          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.

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          Author and article information

          Journal
          Cell
          Cell
          Elsevier BV
          1097-4172
          0092-8674
          Sep 19 2008
          : 134
          : 6
          Affiliations
          [1 ] Department of Physiology, Howard Hughes Medical Institute, University of California San Francisco, San Francisco, CA 94143, USA.
          Article
          S0092-8674(08)01122-7 HHMIMS74760
          10.1016/j.cell.2008.09.003
          2651354
          18805094
          3aa15f32-9ee9-4f9b-8e55-384b713ade77
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