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Anoctamin 6 mediates effects essential for innate immunity downstream of P2X7 receptors in macrophages

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  • Jiraporn Ousingsawat

    (Physiological Institute, University of Regensburg, Universitätsstraße 31)

  • Podchanart Wanitchakool

    (Physiological Institute, University of Regensburg, Universitätsstraße 31)

  • Arthur Kmit

    (Physiological Institute, University of Regensburg, Universitätsstraße 31)

  • Ana M. Romao

    (Physiological Institute, University of Regensburg, Universitätsstraße 31)

  • Walailak Jantarajit

    (Physiological Institute, University of Regensburg, Universitätsstraße 31)

  • Rainer Schreiber

    (Physiological Institute, University of Regensburg, Universitätsstraße 31)

  • Karl Kunzelmann

    (Physiological Institute, University of Regensburg, Universitätsstraße 31)

Abstract

Purinergic P2X7 receptors (P2X7R) are fundamental to innate immune response. In macrophages, transient stimulation of P2X7R activates several transport mechanisms and induces the scrambling of phospholipids with subsequent membrane blebbing and apoptosis. These processes support phagocytosis and subsequent killing of phagocytosed bacteria. Here we demonstrate that the stimulation of P2X7 receptors activates anoctamin 6 (ANO6, TMEM16F), a protein that functions as Ca2+ dependent phospholipid scramblase and Ca2+-activated Cl− channel. Inhibition or knockdown of ANO6 attenuates ATP-induced cell shrinkage, cell migration and phospholipid scrambling. In mouse macrophages, Ano6 produces large ion currents by stimulation of P2X7 receptors and contributes to ATP-induced membrane blebbing and apoptosis, which is largely reduced in macrophages from Ano6−/− mice. ANO6 supports bacterial phagocytosis and killing by mouse and human THP-1 macrophages. Our data demonstrate that anoctamin 6 is an essential component of the immune defense by macrophages.

Suggested Citation

  • Jiraporn Ousingsawat & Podchanart Wanitchakool & Arthur Kmit & Ana M. Romao & Walailak Jantarajit & Rainer Schreiber & Karl Kunzelmann, 2015. "Anoctamin 6 mediates effects essential for innate immunity downstream of P2X7 receptors in macrophages," Nature Communications, Nature, vol. 6(1), pages 1-10, May.
    • Handle: RePEc:nat:natcom:v:6:y:2015:i:1:d:10.1038_ncomms7245
    DOI: 10.1038/ncomms7245
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