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

123Citations
Citations of this article
108Readers
Mendeley users who have this article in their library.

This article is free to access.

Abstract

Purinergic P2X7 receptors (P2X7R) are fundamental to innate immune response. In macrophages, transient stimulation of P2X7 R 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.

Cite

CITATION STYLE

APA

Ousingsawat, J., Wanitchakool, P., Kmit, A., Romao, A. M., Jantarajit, W., Schreiber, R., & Kunzelmann, K. (2015). Anoctamin 6 mediates effects essential for innate immunity downstream of P2X7 receptors in macrophages. Nature Communications, 6. https://doi.org/10.1038/ncomms7245

Register to see more suggestions

Mendeley helps you to discover research relevant for your work.

Already have an account?

Save time finding and organizing research with Mendeley

Sign up for free