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PI3KC3 complex subunit NRBF2 is required for apoptotic cell clearance to restrict intestinal inflammation by Ming-Yue Wu; Le Liu; Er-Jin Wang; Hai-Tao Xiao; Cui-Zan Cai; Jing Wang; Huanxing Su; Yitao Wang; Jieqiong Tan; Zhuohua Zhang; Juan Wang; Maojing Yao; De-Fang Ouyang; Zhenyu Yue; Min Li; Ye Chen; Zhao-Xiang Bian; Jia-Hong Lu is a Medicine article available to read on EtoBox.
What is PI3KC3 complex subunit NRBF2 is required for apoptotic cell clearance to restrict intestinal inflammation about?
NRBF2, a regulatory subunit of the ATG14-BECN1/Beclin 1-PIK3C3/VPS34 complex, positively regulates macroautophagy/autophagy. In this study, we report that NRBF2 is required for the clearance of apoptotic cells and alleviation of inflammation during colitis in mice. NRBF2-deficient mice displayed much more severe colitis symptoms after the administration of ulcerative colitis inducer, dextran sulfate sodium salt (DSS), accompanied by prominent intestinal inflammation and apoptotic cell accumulation. Interestingly, we found that mice and macrophages displayed impaired apoptotic cell clearance capability, while adoptive transfer of macrophages to mice alleviated DSS-induced colitis lesions. Mechanistically, NRBF2 is required for the generation of the active form of RAB7 to promote the fusion between phagosomes containing engulfed apoptotic cells and lysosomes via interacting with the MON1-CCZ1 complex and regulating the guanine nucleotide exchange factor (GEF) activity of the complex. Evidence from clinical samples further reveals the physiological role of NRBF2 in maintaining intestinal homeostasis. In biopsies of UC patient colon, we observed upregulated NRBF2 in the colon macrophag
Who reads PI3KC3 complex subunit NRBF2 is required for apoptotic cell clearance to restrict intestinal inflammation?
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- Author
- Ming-Yue Wu; Le Liu; Er-Jin Wang; Hai-Tao Xiao; Cui-Zan Cai; Jing Wang; Huanxing Su; Yitao Wang; Jieqiong Tan; Zhuohua Zhang; Juan Wang; Maojing Yao; De-Fang Ouyang; Zhenyu Yue; Min Li; Ye Chen; Zhao-Xiang Bian; Jia-Hong Lu
- Publisher
- Landes Bioscience; Informa UK Limited (ISSN 1554-8627)
- Published
- 2020
- Language
- EN
- Field
- Medicine (Health Sciences)