Ousingsawat, Jiraporn and Wanitchakool, Podchanart and Kmit, Arthur and Romao, Ana M. and Jantarajit, Walailak and Schreiber, Rainer and Kunzelmann, Karl (2015) Anoctamin 6 mediates effects essential for innate immunity downstream of P2X(7) receptors in macrophages. NATURE COMMUNICATIONS, 6: 6245. ISSN 2041-1723,
Full text not available from this repository. (Request a copy)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.
| Item Type: | Article |
|---|---|
| Uncontrolled Keywords: | P2X7 RECEPTOR; PHOSPHATIDYLSERINE EXPOSURE; LARGE MOLECULES; PORE FORMATION; ACTIVATION; CHANNEL; DEATH; TMEM16F; EXPRESSION; CHLORIDE; |
| Subjects: | 500 Science > 570 Life sciences |
| Divisions: | Biology, Preclinical Medicine > Institut für Physiologie > Prof. Dr. Karl Kunzelmann |
| Depositing User: | Dr. Gernot Deinzer |
| Date Deposited: | 24 Jul 2019 13:33 |
| Last Modified: | 24 Jul 2019 13:33 |
| URI: | https://pred.uni-regensburg.de/id/eprint/6011 |
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