TMEM16 proteins produce volume-regulated chloride currents that are reduced in mice lacking TMEM16A

Joana Almaca, Yuemin Tian, Fadi Aldehni, Jiraporn Ousingsawat, Patthara Kongsuphol, Jason R. Rock, Brian D. Harfe, Rainer Schreiber, Karl Kunzelmann

Research output: Contribution to journalArticle

124 Citations (Scopus)

Abstract

All vertebrate cells regulate their cell volume by activating chloride channels of unknown molecular identity, thereby activating regulatory volume decrease. We show that the Ca2+-activated Cl- channel TMEM16A together with other TMEM16 proteins are activated by cell swelling through an autocrine mechanism that involves ATP release and binding to purinergic P2Y2 receptors. TMEM16A channels are activated by ATP through an increase in intracellular Ca2+ and a Ca2+-independent mechanism engaging extracellular-regulated protein kinases (ERK1/2). The ability of epithelial cells to activate a Cl- conductance upon cell swelling, and to decrease their cell volume (regulatory volume decrease) was dependent on TMEM16 proteins. Activation of ICl,swell was reduced in the colonic epithelium and in salivary acinar cells from mice lacking expression of TMEM16A. Thus TMEM16 proteins appear to be a crucial component of epithelial volume-regulated Cl- channels and may also have a function during proliferation and apoptotic cell death.

Original languageEnglish (US)
Pages (from-to)28571-28578
Number of pages8
JournalJournal of Biological Chemistry
Volume284
Issue number42
DOIs
StatePublished - Oct 16 2009
Externally publishedYes

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Chlorides
Cell Size
Swelling
Adenosine Triphosphate
Purinergic P2Y2 Receptors
Chloride Channels
Proteins
Acinar Cells
Cell death
Protein Kinases
Vertebrates
Cell Death
Epithelium
Epithelial Cells
Chemical activation

ASJC Scopus subject areas

  • Biochemistry
  • Cell Biology
  • Molecular Biology

Cite this

Almaca, J., Tian, Y., Aldehni, F., Ousingsawat, J., Kongsuphol, P., Rock, J. R., ... Kunzelmann, K. (2009). TMEM16 proteins produce volume-regulated chloride currents that are reduced in mice lacking TMEM16A. Journal of Biological Chemistry, 284(42), 28571-28578. https://doi.org/10.1074/jbc.M109.010074

TMEM16 proteins produce volume-regulated chloride currents that are reduced in mice lacking TMEM16A. / Almaca, Joana; Tian, Yuemin; Aldehni, Fadi; Ousingsawat, Jiraporn; Kongsuphol, Patthara; Rock, Jason R.; Harfe, Brian D.; Schreiber, Rainer; Kunzelmann, Karl.

In: Journal of Biological Chemistry, Vol. 284, No. 42, 16.10.2009, p. 28571-28578.

Research output: Contribution to journalArticle

Almaca, J, Tian, Y, Aldehni, F, Ousingsawat, J, Kongsuphol, P, Rock, JR, Harfe, BD, Schreiber, R & Kunzelmann, K 2009, 'TMEM16 proteins produce volume-regulated chloride currents that are reduced in mice lacking TMEM16A', Journal of Biological Chemistry, vol. 284, no. 42, pp. 28571-28578. https://doi.org/10.1074/jbc.M109.010074
Almaca, Joana ; Tian, Yuemin ; Aldehni, Fadi ; Ousingsawat, Jiraporn ; Kongsuphol, Patthara ; Rock, Jason R. ; Harfe, Brian D. ; Schreiber, Rainer ; Kunzelmann, Karl. / TMEM16 proteins produce volume-regulated chloride currents that are reduced in mice lacking TMEM16A. In: Journal of Biological Chemistry. 2009 ; Vol. 284, No. 42. pp. 28571-28578.
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