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Published Online September 4, 2008
Science DOI: 10.1126/science.1163518

Reports

Submitted on July 21, 2008
Accepted on August 28, 2008

TMEM16A, A Membrane Protein Associated With Calcium-Dependent Chloride Channel Activity

Antonella Caputo 1, Emanuela Caci 1, Loretta Ferrera 1, Nicoletta Pedemonte 2, Cristina Barsanti 1, Elvira Sondo 1, Ulrich Pfeffer 3, Roberto Ravazzolo 1, Olga Zegarra-Moran 1, Luis J. V. Galietta 4*

1 Laboratorio di Genetica Molecolare, Istituto Giannina Gaslini, Genova, Italy.
2 Centro di Biotecnologie Avanzate, Genova, Italy.
3 National Cancer Research Institute, Genova, Italy.
4 Laboratorio di Genetica Molecolare, Istituto Giannina Gaslini, Genova, Italy.; Centro di Biotecnologie Avanzate, Genova, Italy.

* To whom correspondence should be addressed.
Luis J. V. Galietta , E-mail: galietta{at}unige.it

Calcium-dependent chloride channels (CaCC) are required for normal electrolyte and fluid secretion, olfactory perception, neuronal and smooth muscle excitability. The molecular identity of these membrane proteins is still unclear. Treatment of bronchial epithelial cells with interleukin-4 (IL-4) causes increased calcium-dependent chloride channel activity, presumably by regulating expression of the corresponding genes. We have now performed a global gene expression analysis to identify membrane proteins that are regulated by IL-4. Transfection of epithelial cells with specific siRNA against each of these proteins shows that TMEM16A, a member of a family of putative plasma membrane proteins with unknown function, is associated with calcium-dependent chloride current, as measured by halide-sensitive fluorescent proteins, short-circuit current, and patch-clamp techniques. Our results indicate that TMEM16A is an intrinsic constituent of the calcium-dependent chloride channel. Identification of a new family of membrane proteins associated with chloride channel function will improve our understanding of chloride transport physiopathology and allow development for novel pharmacological tools useful for basic research and drug development.


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