STING trafficking as a new dimension of immune signaling.

STING trafficking as a new dimension of immune signaling.
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DOI:
10.1084/jem.20220990
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发表时间:
2023-03-06
期刊:
The Journal of experimental medicine
影响因子:
--
通讯作者:
--
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其他
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STING信号是多种自体炎症和神经退行性疾病的中心。作者回顾了刺痛运输如何影响信号传递,提出了一个紧张性刺痛信号模型,并讨论了失调的刺痛运输与神经退行性疾病之间的新出现的联系。CGAS-STING通路是一条进化上保守的免疫信号通路,对微生物防御至关重要。与在很大程度上依赖于信号事件的固定级联的其他先天免疫途径不同,刺痛在细胞中具有高度的移动性。刺痛在内质网上被激活,但只有在它到达高尔基体后才会发出信号,然后它会被溶酶体迅速降解。通过分泌途径进行的刺痛运输的每一步都受到宿主因素的调节。通过COPI、COPII和笼蛋白包裹的囊泡运输动态平衡的刺痛对于维持基线组织和细胞免疫是重要的。异常的囊泡运输或溶酶体功能障碍通过刺痛产生免疫信号,这通常会导致小鼠和人类的组织病理。许多由人口贩运介导的刺痛信号疾病似乎会影响中枢神经系统,导致神经退化。因此,刺痛贩运引入了免疫信号的新维度,可能在人类疾病中具有广泛的影响。
STING signaling is at the center of multiple autoinflammatory and neurodegenerative diseases. The authors review how STING trafficking influences signaling, propose a model of tonic STING signaling, and discuss an emerging link between dysregulated STING trafficking and neurodegenerative disease. The cGAS–STING pathway is an evolutionarily conserved immune signaling pathway critical for microbial defense. Unlike other innate immune pathways that largely rely on stationary cascades of signaling events, STING is highly mobile in the cell. STING is activated on the ER, but only signals after it arrives on the Golgi, and then it is quickly degraded by the lysosome. Each step of STING trafficking through the secretory pathway is regulated by host factors. Homeostatic STING trafficking via COPI-, COPII-, and clathrin-coated vesicles is important for maintaining baseline tissue and cellular immunity. Aberrant vesicular trafficking or lysosomal dysfunction produces an immune signal through STING, which often leads to tissue pathology in mice and humans. Many trafficking-mediated diseases of STING signaling appear to impact the central nervous system, leading to neurodegeneration. Therefore, STING trafficking introduces a new dimension of immune signaling that likely has broad implications in human disease.
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