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

Jiraporn Ousingsawat, Podchanart Wanitchakool, Arthur Kmit, Ana M. Romao, Walailak Jantarajit, Rainer Schreiber and Karl Kunzelmann ()
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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

Nature Communications, 2015, vol. 6, issue 1, 1-10

Abstract: 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.

Date: 2015
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Persistent link: https://EconPapers.repec.org/RePEc:nat:natcom:v:6:y:2015:i:1:d:10.1038_ncomms7245

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DOI: 10.1038/ncomms7245

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