Cellular volume regulation by anoctamin 6: Ca2+, phospholipase A2 and osmosensing
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  • 作者:Lalida Sirianant ; Jiraporn Ousingsawat…
  • 关键词:TMEM16F ; Anoctamin 6 ; Volume regulation ; Regulatory volume decrease ; RVD ; Volume ; regulated anion channel ; VRAC ; Apoptosis
  • 刊名:Pfl¨¹gers Archiv - European Journal of Physiology
  • 出版年:2016
  • 出版时间:February 2016
  • 年:2016
  • 卷:468
  • 期:2
  • 页码:335-349
  • 全文大小:5,350 KB
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  • 作者单位:Lalida Sirianant (1)
    Jiraporn Ousingsawat (1)
    Podchanart Wanitchakool (1)
    Rainer Schreiber (1)
    Karl Kunzelmann (1)

    1. Institut für Physiologie, Universität Regensburg, Universitätsstraße 31, 93053, Regensburg, Germany
  • 刊物主题:Human Physiology;
  • 出版者:Springer Berlin Heidelberg
  • ISSN:1432-2013
文摘
During cell swelling, Cl− channels are activated to lower intracellular Cl− concentrations and to reduce cell volume, a process termed regulatory volume decrease (RVD). We show that anoctamin 6 (ANO6; TMEM16F) produces volume-regulated anion currents and controls cell volume in four unrelated cell types. Volume regulation is compromised in freshly isolated intestinal epithelial cells from Ano6−/− mice and also in lymphocytes from a patient lacking expression of ANO6. Ca2+ influx is activated and thus ANO6 is stimulated during cell swelling by local Ca2+ increase probably in functional nanodomains near the plasma membrane. This leads to stimulation of phospholipase A2 (PLA2) and generation of plasma membrane lysophospholipids, which activates ANO6. Direct application of lysophospholipids also activates an anion current that is inhibited by typical ANO6 blocker. An increase in intracellular Ca2+ supports activation of ANO6, but is not required when PLA2 is fully activated, while re-addition of arachidonic acid completely blocked ANO6. Moreover, ANO6 is activated by low intracellular Cl− concentrations and may therefore operate as a cellular osmosensor. High intracellular Cl− concentration inhibits ANO6 and activation by PLA2. Taken together, ANO6 supports volume regulation and volume activation of anion currents by action as a Cl− channel or by scrambling membrane phospholipids. Thereby, it may support the function of LRRC8 proteins.
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