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):

ORGANISM(S): Mus Musculus (mouse)

TISSUE(S): Cell Culture

SUBMITTER: James Wright  

LAB HEAD: Jyoti Choudhary

PROVIDER: PXD024659 | Pride | 2023-03-11

REPOSITORIES: Pride