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TMEM16A, A Membrane Protein Associated with Calcium-Dependent Chloride Channel Activity
Antonella Caputo,1Emanuela Caci,1Loretta Ferrera,1Nicoletta Pedemonte,2Cristina Barsanti,1Elvira Sondo,1Ulrich Pfeffer,3Roberto Ravazzolo,1Olga Zegarra-Moran,1Luis J. V. Galietta1,2*
Calcium-dependent chloride channels are required for normalelectrolyte and fluid secretion, olfactory perception, and neuronaland smooth muscle excitability. The molecular identity of thesemembrane proteins is still unclear. Treatment of bronchial epithelialcells with interleukin-4 (IL-4) causes increased calcium-dependentchloride channel activity, presumably by regulating expressionof the corresponding genes. We performed a global gene expressionanalysis to identify membrane proteins that are regulated byIL-4. Transfection of epithelial cells with specific small interferingRNA against each of these proteins shows that TMEM16A, a memberof a family of putative plasma membrane proteins with unknownfunction, is associated with calcium-dependent chloride current,as measured with halide-sensitive fluorescent proteins, short-circuitcurrent, and patch-clamp techniques. Our results indicate thatTMEM16A is an intrinsic constituent of the calcium-dependentchloride channel. Identification of a previously unknown familyof membrane proteins associated with chloride channel functionwill improve our understanding of chloride transport physiopathologyand allow for the development of pharmacological tools usefulfor 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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