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

By Björn C. Schroeder, T. Cheng, Y. Jan, L. Jan. Cell, 2008

1,156 citations recorded by the source corpus.

SUMMARY 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 oocyte membrane. None of the known molecular candidates share properties characteristic of most CaCCs in native cells. Using Axolotl oocytes as 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.

Subfields: Cellular and Molecular Neuroscience, Molecular Biology

View Paper: https://www.semanticscholar.org/paper/0cea7a2f9e0d156af3ce6ff3ebf9b07fbd98a90d

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In Cellular and Molecular Neuroscience

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Citations in the corpus

Handbook of ion channels (2015, methodology): “There have also been reports that the anionic selectivity of TMEM16A and B shifts over the course of channel activation (Sagheddu et al., 2010; Schroeder et al., 2008).”
A protein kinase-phosphatase pair interacts with an ion channel to regulate ABA signaling in plant guard cells (2009, background): “Under these conditions, the endogenous calcium-activated chloride channel was not active (34).”