RRC ID 58368
著者 Ryoden Y, Fujii T, Segawa K, Nagata S.
タイトル Functional Expression of the P2X7 ATP Receptor Requires Eros.
ジャーナル J Immunol
Abstract 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 Eros-null mouse T cell line lost the ability to expose PtdSer, to scramble phospholipids, and to internalize a dye YO-PRO-1 and Ca2+ ions. Eros-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.
巻・号 204(3)
ページ 559-568
公開日 2020-2-1
DOI 10.4049/jimmunol.1900448
PII jimmunol.1900448
PMID 31862710
MeSH Adenosine Triphosphate / metabolism Animals Calcium Signaling Gene Knockdown Techniques Humans Interleukin-1beta / metabolism Macrophages / immunology* Membrane Proteins / genetics Membrane Proteins / metabolism* Mice Mutation / genetics Phagocytosis / genetics Phosphatidylserines / metabolism Receptors, Purinergic P2X7 / genetics Receptors, Purinergic P2X7 / metabolism* THP-1 Cells
IF 4.718
引用数 0
リソース情報
遺伝子材料 pCMV-VSV-G-RSV-Rev (RDB04393) pCMV-VSV-G (RDB04392)