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

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

Research output: Contribution to journalArticle

129 Scopus citations

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

ASJC Scopus subject areas

  • Biochemistry
  • Molecular Biology
  • Cell Biology

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    Almaça, J., Tian, Y., Aldehni, F., Ousingsawat, J., Kongsuphol, P., Rock, J. R., Harfe, B. D., Schreiber, 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