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Originally published in Science Express on 4 September 2008
Science 24 October 2008:
Vol. 322. no. 5901, pp. 590 - 594
DOI: 10.1126/science.1163518
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Reports

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. Galietta1,2*

Calcium-dependent chloride channels are required for normal electrolyte and fluid secretion, olfactory perception, and 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 performed a global gene expression analysis to identify membrane proteins that are regulated by IL-4. Transfection of epithelial cells with specific small interfering RNA 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 with 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 previously unknown family of membrane proteins associated with chloride channel function will improve our understanding of chloride transport physiopathology and allow for the development of pharmacological tools useful for basic research and drug development.

1 Laboratorio di Genetica Molecolare, Istituto Giannina Gaslini, Genova 16148, Italy.
2 Centro di Biotecnologie Avanzate, Genova 16132, Italy.
3 National Cancer Research Institute, Genova 16132, Italy.

* To whom correspondence should be addressed. E-mail: galietta{at}unige.it

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Science. ISSN 0036-8075 (print), 1095-9203 (online)