EROS is a selective chaperone regulating the phagocyte NADPH oxidase and purinergic signalling
EROS is a selective chaperone regulating the phagocyte NADPH oxidase and purinergic signalling
EROS (Essential for Reactive Oxygen Species) protein is indispensable for expression of gp91phox, the catalytic core of the phagocyte NADPH oxidase. EROS deficiency in humans is a novel cause of the severe immunodeficiency, chronic granulomatous disease (CGD), but its mechanism of action was unknown until now. We elucidate the role of EROS, showing it acts at the earliest stages of gp91phox maturation. It binds the immature 58kDa gp91phox directly, preventing gp91phox degradation and allowing glycosylation via the oligosaccharyltransferase (OST) machinery and the incorporation of the heme prosthetic groups essential for catalysis. EROS also regulates the purine receptors P2X7 and P2X1 through direct interactions and P2X7 is almost absent in EROS deficient mouse and human primary cells. Accordingly, lack of EROS results in markedly abnormal P2X7 signalling, inflammasome activation and T cell responses. The loss of both ROS and P2X7 signalling leads to resistance to influenza infection. Our work identifies EROS as a highly selective chaperone for key proteins in innate and adaptive immunity and a rheostat for immunity to infection. It has profound implications for our understanding of immune physiology, ROS dysregulation and possibly gene therapy.
Randzavola Lyra O、Mortimer Paige M、Garside Emma C、Schejtman Andrea、Spirohn Kerstin、Tolley Charlotte、Brandt Cordelia、Woods Geoff、Sowerby John M、Kiar Cher Shen、Mukhopadhyay Subhankar、Lehner Paul J、Speak Anneliese O、Santilli Giorgia、Bateman Alex、Smith Kenneth G C、Dufficy Elizabeth R、Thomas David C、Matsumoto Misaki、Grainger John Robert、Suresh Shreehari、Dougan Gordon、Williamson James C、Roumelioti Georgia、Santos Celio X.C.、Rae Will M、Chaudhary Jyoti S、Nahorski Mike、Harcourt Katherine、Nichols Esme、Pardo Mercedes、Clare Simon、Magnani Francesca、Calderwood Michael、Yu Lu
基础医学生物化学分子生物学
Randzavola Lyra O,Mortimer Paige M,Garside Emma C,Schejtman Andrea,Spirohn Kerstin,Tolley Charlotte,Brandt Cordelia,Woods Geoff,Sowerby John M,Kiar Cher Shen,Mukhopadhyay Subhankar,Lehner Paul J,Speak Anneliese O,Santilli Giorgia,Bateman Alex,Smith Kenneth G C,Dufficy Elizabeth R,Thomas David C,Matsumoto Misaki,Grainger John Robert,Suresh Shreehari,Dougan Gordon,Williamson James C,Roumelioti Georgia,Santos Celio X.C.,Rae Will M,Chaudhary Jyoti S,Nahorski Mike,Harcourt Katherine,Nichols Esme,Pardo Mercedes,Clare Simon,Magnani Francesca,Calderwood Michael,Yu Lu.EROS is a selective chaperone regulating the phagocyte NADPH oxidase and purinergic signalling[EB/OL].(2025-03-28)[2025-08-02].https://www.biorxiv.org/content/10.1101/2021.09.14.460103.点此复制
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