title: TMEM16A, a membrane protein associated with calcium-dependent chloride channel activity.
abstract: 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.
authors.affiliation: Laboratorio di Genetica Molecolare, Istituto Giannina Gaslini, Genova 16148, Italy.
authors.forename: Antonella
authors.initials: A
authors.lastname: Caputo
authors.forename: Emanuela
authors.initials: E
authors.lastname: Caci
authors.forename: Loretta
authors.initials: L
authors.lastname: Ferrera
authors.forename: Nicoletta
authors.initials: N
authors.lastname: Pedemonte
authors.forename: Cristina
authors.initials: C
authors.lastname: Barsanti
authors.forename: Elvira
authors.initials: E
authors.lastname: Sondo
authors.forename: Ulrich
authors.initials: U
authors.lastname: Pfeffer
authors.forename: Roberto
authors.initials: R
authors.lastname: Ravazzolo
authors.forename: Olga
authors.initials: O
authors.lastname: Zegarra-Moran
authors.forename: Luis J V
authors.initials: LJ
authors.lastname: Galietta
mesh_terms: D017398:Alternative Splicing; D000595:Amino Acid Sequence; D000818:Animals; D000075369:Anoctamin-1; D001980:Bronchi / Q000166:cytology / Q000378:metabolism*; D002118:Calcium / Q000378:metabolism*; D002460:Cell Line; D002462:Cell Membrane / Q000378:metabolism*; D002478:Cells, Cultured; D018118:Chloride Channels / Q000378:metabolism*; D002712:Chlorides / Q000378:metabolism*; D004847:Epithelial Cells / Q000378:metabolism; D006801:Humans; D015847:Interleukin-4 / Q000378:metabolism; D008565:Membrane Proteins / Q000737:chemistry / Q000235:genetics / Q000378:metabolism*; D008969:Molecular Sequence Data; D009363:Neoplasm Proteins / Q000737:chemistry / Q000235:genetics / Q000378:metabolism*; D020411:Oligonucleotide Array Sequence Analysis; D018408:Patch-Clamp Techniques; D034741:RNA, Small Interfering; D020545:Respiratory Mucosa / Q000166:cytology / Q000378:metabolism; D014162:Transfection
chemical_list: C476213:ANO1 protein, human; D000075369:Anoctamin-1; D018118:Chloride Channels; D002712:Chlorides; C508598:IL4 protein, human; D008565:Membrane Proteins; D009363:Neoplasm Proteins; D034741:RNA, Small Interfering; D015847:Interleukin-4; D002118:Calcium