Expression Cloning of TMEM16A as a Calcium-Activated Chloride Channel Subunit

Cell. 2008 Sep 19;134(6):1019-29. doi: 10.1016/j.cell.2008.09.003.

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.

Publication types

  • Research Support, N.I.H., Extramural
  • Research Support, Non-U.S. Gov't

MeSH terms

  • Ambystoma / genetics
  • Animals
  • Anoctamin-1
  • Anoctamins
  • Cell Line
  • Chloride Channels / antagonists & inhibitors
  • Chloride Channels / genetics*
  • Chloride Channels / metabolism*
  • Cloning, Molecular*
  • Humans
  • Mice
  • Molecular Sequence Data
  • Oocytes / metabolism
  • Xenopus Proteins / antagonists & inhibitors
  • Xenopus Proteins / genetics*
  • Xenopus Proteins / metabolism*
  • Xenopus laevis / genetics
  • Xenopus laevis / metabolism*

Substances

  • ANO1 protein, mouse
  • ANO2 protein, mouse
  • Anoctamin-1
  • Anoctamins
  • Chloride Channels
  • Xenopus Proteins
  • xANO2 protein, Xenopus

Associated data

  • GENBANK/EU367938