PI3KC3 complex subunit NRBF2 is required for apoptotic cell clearance to restrict intestinal inflammation

Wu, Mingyue; Liu, Le; Wang, Er-Jin; Xiao, Haitao; Cai, Cui-Zan; Wang, Jing; Su, Huanxing; Wang, Ying; Tan, Jieqiong; Zhang, Zhuohua; Wang, Juan; Yao, Maojing; Ouyang, Defang; Yue, Zhenyu; Li, Min; Chen, Ye; Bian, Zhaoxiang; Lu, Jiahong

doi:10.1080/15548627.2020.1741332

Cited by 54 publications

(49 citation statements)

References 52 publications

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“…It has long been established that small GTPase Rab7 is essential for the fusion between late-stage phagosomes and lysosomes, and consequently, for the function of phagocytes in both pathogen and apoptotic cell clearance ( 33 , 47 , 48 ). Several pathogens have been described to inhibit Rab7 recruitment in order to replicate and survive within phagosomes, and has been comprehensively reviewed ( 49 ).…”

Section: Marking the Membranes: Small Rab Gtpasesmentioning

confidence: 99%

“…In a C. elegans model of apoptotic cell removal, the siRNA-mediated knockdown of Rab7 contributed to the accumulation of apoptotic bodies in phagosomes ( 34 ). Similarly, in an in vivo model of murine ulcerative colitis, inflammation and disease severity was exacerbated when Rab7 activation and recruitment was impaired in macrophages, reportedly due to an accumulation of apoptotic epithelial cells in the colon ( 48 ).…”

Section: Marking the Membranes: Small Rab Gtpasesmentioning

confidence: 99%

“…Phosphatidylinositol-3-phosphates (PI3P) on early phagosomes have been proposed to both recruit Mon1-Ccz1 to early-to-late transitional phagosomes and activate the GEF activity of the complex ( Figure 2Ai ) ( 48 , 53 ). Recently, nuclear receptor binding factor 2 (NRBF2), a component of the class III phosphoinositide 3-kinase (PI3KIII)/vacuolar sorting protein (Vps) 34 complex that generates PI3P on phagosomes, has been implicated to regulate the function of the Mon1-Ccz1 complex during apoptotic cell clearance in macrophages ( 48 ). NRBF2 is a binding partner of the catalytic subunit of the PI3KIII/Vps34 complex and can facilitate the interaction between PI3KIII/Vps34 and Mon1-Ccz1 ( Figure 2Ai ).…”

Section: Marking the Membranes: Small Rab Gtpasesmentioning

confidence: 99%

“…Through this interaction, NRBF2 may bring the PI3KIII/Vps34 complex to phagosomes or support the activation of PI3KIII/Vps34, thereby generating PI3P to activate the GEF activity of the Mon1-Ccz1 complex. Further evidence that NRBF2 modulates the activity of the Mon1-Ccz1complex is provided by an observed loss of GTP-bound Rab7 around phagosomes as well as delayed Rab7 recruitment in NRBF2-knockout macrophages ( 48 ). Lou and colleagues ( 54 ) have proposed that another factor, sorting nexin 10 (Snx10), can promote the recruitment of Mon1-Ccz1 to early endosomes and phagosomes to mediate Rab7 recruitment ( Figure 2Ai ).…”

Section: Marking the Membranes: Small Rab Gtpasesmentioning

confidence: 99%

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Better Together: Current Insights Into Phagosome-Lysosome Fusion

Nguyen

Yates

2021

Front. Immunol.

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Following phagocytosis, the nascent phagosome undergoes maturation to become a phagolysosome with an acidic, hydrolytic, and often oxidative lumen that can efficiently kill and digest engulfed microbes, cells, and debris. The fusion of phagosomes with lysosomes is a principal driver of phagosomal maturation and is targeted by several adapted intracellular pathogens. Impairment of this process has significant consequences for microbial infection, tissue inflammation, the onset of adaptive immunity, and disease. Given the importance of phagosome-lysosome fusion to phagocyte function and the many virulence factors that target it, it is unsurprising that multiple molecular pathways have evolved to mediate this essential process. While the full range of these pathways has yet to be fully characterized, several pathways involving proteins such as members of the Rab GTPases, tethering factors and SNAREs have been identified. Here, we summarize the current state of knowledge to clarify the ambiguities in the field and construct a more comprehensive phagolysosome formation model. Lastly, we discuss how other cellular pathways help support phagolysosome biogenesis and, consequently, phagocyte function.

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Section: Marking the Membranes: Small Rab Gtpasesmentioning

confidence: 99%

Section: Marking the Membranes: Small Rab Gtpasesmentioning

confidence: 99%

Section: Marking the Membranes: Small Rab Gtpasesmentioning

confidence: 99%

Section: Marking the Membranes: Small Rab Gtpasesmentioning

confidence: 99%

See 2 more Smart Citations

Better Together: Current Insights Into Phagosome-Lysosome Fusion

Nguyen

Yates

2021

Front. Immunol.

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“…Next, Bcl-2-interacting protein (BECLIN)-1 is phosphorylated by ULK1 and acts as a scaffold to form the class III phosphatidylinositol-3 kinase (PI3K) complex (Fracchiolla et al, 2020). During this process, the ultraviolet radiation resistance-associated gene proteins ATG14 and p150 bind to BECLIN-1 to facilitate its interaction with vacuolar protein sorting protein 34 (VPS34) and phagophore formation (Boukhalfa et al, 2020;Wu M. Y. et al, 2020). Vesicle elongation is induced by two ubiquitin-like conjugating systems, ATG12-ATG5 and microtubule-associated protein 1A/1B-light chain 3-II (LC3-II), together with p62 and other molecules, resulting in the formation of a compartment called the autophagosome (Lystad et al, 2019;Yan et al, 2019).…”

Section: Introductionmentioning

confidence: 99%

Rheostatic Balance of Circadian Rhythm and Autophagy in Metabolism and Disease

Wang

Cai

et al. 2020

Front. Cell Dev. Biol.

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Circadian rhythms are physical, behavioral and environmental cycles that respond primarily to light and dark, with a period of time of approximately 24 h. The most essential physiological functions of mammals are manifested in circadian rhythm patterns, including the sleep-wake cycle and nutrient and energy metabolism. Autophagy is a conserved biological process contributing to nutrient and cellular homeostasis. The factors affecting autophagy are numerous, such as diet, drugs, and aging. Recent studies have indicated that autophagy is activated rhythmically in a clock-dependent manner whether the organism is healthy or has certain diseases. In addition, autophagy can affect circadian rhythm by degrading circadian proteins. This review discusses the interaction and mechanisms between autophagy and circadian rhythm. Moreover, we introduce the molecules influencing both autophagy and circadian rhythm. We then discuss the drugs affecting the circadian rhythm of autophagy. Finally, we present the role of rhythmic autophagy in nutrient and energy metabolism and its significance in physiology and metabolic disease.

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Picroside III, an Active Ingredient of Picrorhiza scrophulariiflora, Ameliorates Experimental Colitis by Protecting Intestinal Barrier Integrity

Huan

Gao

et al. 2023

Chemistry & Biodiversity

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This study aims to explore the protective effects of Picroside III, an active ingredient of Picrorhiza scrophulariiflora, on the intestinal epithelial barrier in tumor necrosis factor‐α (TNF‐α) induced Caco‐2 cells and dextran sulfate sodium (DSS) induced colitis in mice. Results show that Picroside III significantly alleviated clinical signs of colitis including body weight loss, disease activity index increase, colon shortening, and colon tissue damage. It also increased claudin‐3, ZO‐1 and occludin expressions and decreased claudin‐2 expression in the colon tissues of mice with colitis. In vitro, Picroside III also significantly promoted wound healing, decreased the permeability of cell monolayer, upregulated the expressions of claudin‐3, ZO‐1 and occludin and downregulated the expression of claudin‐2 in TNF‐α treated Caco‐2 cells. Mechanism studies show that Picroside III significantly promoted AMP‐activated protein kinase (AMPK) phosphorylation in vitro and in vivo, and blockade with AMPK could significantly attenuate the upregulation of Picroside III in ZO‐1 and occludin expressions and the downregulation of claudin‐2 expression in TNF‐α treated Caco‐2 cells. In conclusion, this study demonstrates that Picroside III attenuated DSS‐induced colitis by promoting colonic mucosal wound healing and epithelial barrier function recovery via the activation of AMPK.

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PI3KC3 complex subunit NRBF2 is required for apoptotic cell clearance to restrict intestinal inflammation

Cited by 54 publications

References 52 publications

Better Together: Current Insights Into Phagosome-Lysosome Fusion

Better Together: Current Insights Into Phagosome-Lysosome Fusion

Rheostatic Balance of Circadian Rhythm and Autophagy in Metabolism and Disease

Picroside III, an Active Ingredient of Picrorhiza scrophulariiflora, Ameliorates Experimental Colitis by Protecting Intestinal Barrier Integrity

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