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Expression Cloning of TMEM16A as a Calcium-Activated Chloride Channel Subunit
Open accessAbstract
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.
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Cited by
Role of CFTR in epithelial physiology
Saint-Criq, V., & Gray, M. A. (2017) · Cellular and Molecular Life Sciences · doi:10.1007/s00018-016-2391-y · Cited by 433
Calcium-dependent Phospholipid Scramblase Activity of TMEM16 Protein Family Members
Suzuki, J., Fujii, T., Imao, T., Ishihara, K., Kuba, H., & Nagata, S. (2013) · Journal of Biological Chemistry · doi:10.1074/jbc.m113.457937 · Cited by 371
Namkung, W., Phuan, P.-W., & Verkman, A. S. (2011) · Journal of Biological Chemistry · doi:10.1074/jbc.m110.175109 · Cited by 353
Cryo-EM structures of the TMEM16A calcium-activated chloride channel
Dang, S., Feng, S., Tien, J., Peters, C. J., Bulkley, D., Lolicato, M., Zhao, J., Zuberbühler, K., Ye, W., Qi, L., et al. (2017) · Nature · doi:10.1038/nature25024 · Cited by 333
Self-citationPhosphoinositides regulate ion channels
Hille, B., Dickson, E. J., Kruse, M., Vivas, O., & Suh, B.-C. (2015) · Biochimica et Biophysica Acta (BBA) - Molecular and Cell Biology of Lipids · doi:10.1016/j.bbalip.2014.09.010 · Cited by 312
Metadata
- Authors
- Schroeder, B. C., Cheng, T., Jan, Y. N., & Jan, L. Y.
- Venue
- Cell
- Publisher
- Elsevier BV
- Published
- 2008-09
- Volume
- 134
- Issue
- 6
- Pages
- 1019-1029
- ISSN
- 0092-8674 (ISSN-L)
- OpenAlex
- W2092868876
- Cited by
- 1,148
- References
- 0
- FWCI
- 22.83
- Type
- journal article
- Language
- en
- Open access
- bronze
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- Schroeder, B. C., Cheng, T., Jan, Y. N., & Jan, L. Y. (2008). Expression Cloning of TMEM16A as a Calcium-Activated Chloride Channel Subunit. Cell. https://doi.org/10.1016/j.cell.2008.09.003
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