Functional Expression of the P2X7 ATP Receptor Requires Eros

• Published in: The Journal of immunology (1950) Vol. 204; no. 3; pp. 559 - 568
• Main Authors: Ryoden, Yuta, Fujii, Toshihiro, Segawa, Katsumori, Nagata, Shigekazu
• Format: Journal Article
• Language: English
• Published: United States 01.02.2020
• ISSN: 0022-1767; 1550-6606
• DOI: 10.4049/jimmunol.1900448

In response to extracellular ATP, the purinergic receptor P2X7 mediates various biological processes, including phosphatidylserine (PtdSer) exposure, phospholipid scrambling, dye uptake, ion transport, and IL-1β production. A genome-wide CRISPR screen for molecules responsible for ATP-induced PtdSer exposure identified a transmembrane protein, essential for reactive oxygen species (Eros), as a necessary component for P2X7 expression. An -null mouse T cell line lost the ability to expose PtdSer, to scramble phospholipids, and to internalize a dye YO-PRO-1 and Ca ions. -null mutation abolished the ability of an LPS-primed human THP-1 macrophage cell line and mouse bone marrow-derived macrophages to secrete IL-1β in response to ATP. Eros is localized to the endoplasmic reticulum and functions as a chaperone for NADPH oxidase components. Similarly, Eros at the endoplasmic reticulum transiently associated with P2X7 to promote the formation of a stable homotrimeric complex of P2X7. These results indicated that Eros acts as a chaperone not only for NADPH oxidase, but also for P2X7, and contributes to the innate immune reaction.