TMEM16A, a membrane protein associated with calcium-dependent chloride channel activity

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

Research output: Contribution to journalArticle

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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.

Original languageEnglish
Pages (from-to)590-594
Number of pages5
JournalScience
Volume322
Issue number5901
DOIs
Publication statusPublished - Oct 24 2008

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Calcium Chloride
Chloride Channels
Membrane Proteins
Interleukin-4
Olfactory Perception
Epithelial Cells
Gene Expression
Fluids and Secretions
Patch-Clamp Techniques
Small Interfering RNA
Electrolytes
Transfection
Smooth Muscle
Chlorides
Blood Proteins
Proteins
Cell Membrane
Pharmacology
Research
Pharmaceutical Preparations

ASJC Scopus subject areas

  • General

Cite this

TMEM16A, a membrane protein associated with calcium-dependent chloride channel activity. / Caputo, Antonella; Caci, Emanuela; Ferrera, Loretta; Pedemonte, Nicoletta; Barsanti, Cristina; Sondo, Elvira; Pfeffer, Ulrich; Ravazzolo, Roberto; Zegarra-Moran, Olga; Galietta, Luis J V.

In: Science, Vol. 322, No. 5901, 24.10.2008, p. 590-594.

Research output: Contribution to journalArticle

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AU - Caputo, Antonella

AU - Caci, Emanuela

AU - Ferrera, Loretta

AU - Pedemonte, Nicoletta

AU - Barsanti, Cristina

AU - Sondo, Elvira

AU - Pfeffer, Ulrich

AU - Ravazzolo, Roberto

AU - Zegarra-Moran, Olga

AU - Galietta, Luis J V

PY - 2008/10/24

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N2 - 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.

AB - 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.

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