Proteomics

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EROS/CYBC1 CONTROLS THE PHAGOCYTE RESPIRATORY BURST VIA DIRECT INTERACTION WITH GP91PHOX AND HAS A NOVEL ROLE IN NLRP3 INFLAMMASOME ACTIVATION

ABSTRACT: EROS (Essential for Reactive Oxygen Species) protein (CYBC1) is indispensable for expression of the gp91phox-p22phox heterodimer of the phagocyte NADPH oxidase. EROS deficiency in humans is a novel cause of chronic granulomatous disease (CGD) but its mechanism of action remains unclear. Our work describes how EROS regulates protein abundance and describes novel roles for EROS in innate and adaptive immunity. EROS acts very early in gp91phox maturation, binding the translated 58kDa precursor directly in the endoplasmic reticulum prior to glycosylation and heme incorporation, thus preventing its degradation. Its actions are distinct from that of p22phox, which is required much later in gp91phox biosynthesis. Further, EROS’s ability to regulate p22phox abundance is entirely secondary to its effect on gp91phox. EROS also regulates the expression of other proteins, including the purine receptors P2X7 and P2X1 through direct interactions.

INSTRUMENT(S): Orbitrap Fusion Lumos

ORGANISM(S): Mus Musculus (mouse)

TISSUE(S): Cell Culture

SUBMITTER: James Wright  

LAB HEAD: Jyoti Choudhary

PROVIDER: PXD024659 | Pride | 2023-03-11

REPOSITORIES: Pride

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Dataset's files

Source:
Action DRS
BC17643_01_allbands.msf Msf
BC17643_01_allbands.pdResult Other
BC17643_01_allbands_Proteins.txt Txt
BC17643_02_allbands.msf Msf
BC17643_02_allbands.pdResult Other
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Publications

EROS is a selective chaperone regulating the phagocyte NADPH oxidase and purinergic signalling.

Randzavola Lyra O LO   Mortimer Paige M PM   Garside Emma E   Dufficy Elizabeth R ER   Schejtman Andrea A   Roumelioti Georgia G   Yu Lu L   Pardo Mercedes M   Spirohn Kerstin K   Tolley Charlotte C   Brandt Cordelia C   Harcourt Katherine K   Nichols Esme E   Nahorski Mike M   Woods Geoff G   Williamson James C JC   Suresh Shreehari S   Sowerby John M JM   Matsumoto Misaki M   Santos Celio X C CXC   Kiar Cher Shen CS   Mukhopadhyay Subhankar S   Rae William M WM   Dougan Gordon J GJ   Grainger John J   Lehner Paul J PJ   Calderwood Michael A MA   Choudhary Jyoti J   Clare Simon S   Speak Anneliese A   Santilli Giorgia G   Bateman Alex A   Smith Kenneth G C KGC   Magnani Francesca F   Thomas David C DC  

eLife 20221124

EROS (essential for reactive oxygen species) protein is indispensable for expression of gp91<i>phox</i>, the catalytic core of the phagocyte NADPH oxidase. EROS deficiency in humans is a novel cause of the severe immunodeficiency, chronic granulomatous disease, but its mechanism of action was unknown until now. We elucidate the role of EROS, showing it acts at the earliest stages of gp91<i>phox</i> maturation. It binds the immature 58 kDa gp91<i>phox</i> directly, preventing gp91<i>phox</i> degr  ...[more]

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