由STING诱导的非正规性自调节了内分泌体内稳态
Tuozhi Huang1,2, Chenglong Sun1,2, Fenghe Du1,2,3
1Department of Molecular Biology, University of Texas, Southwestern Medical Center, Dallas, TX 75390-9148.
概括
cGAS-STING通路通过Golgi衍生的囊泡触发非正规的自,激活MiT/TFE转录因子. 这个过程调节了溶酶体生物发生,并影响了帕金森氏症.
科学领域:
- 免疫学 免疫学 免疫学
- 细胞生物学 细胞生物学
- 分子生物学分子生物学
背景情况:
- 这种cGAS-STING通路对于对细胞核DNA的天生的免疫是至关重要的.
- 激活STING会诱导非正规的自,但机制和功能尚不清楚.
- 非正规的自涉及ATG8蛋白与内解体膜的结合.
研究的目的:
- 阐明SING诱导的非正规性自的机制和功能.
- 为了研究通过STING诱导的自细胞调节MiT/TFE转录因子.
- 探索STING诱导的自,LRRK2和内分泌体平衡之间的联系.
主要方法:
- 研究了STING激活对Golgi衍生的囊泡的影响.
- 分析了ATG16L1和V-ATPase参与自的情况.
- 通过mTORC1.1检查了MiT/TFE转录因子的激活和调节.
- 研究了GABARAP脂化及其与FNIP-folliculin复合物的相互作用.
- 评估了LRRK2激活和ALIX介导的ESCRT招聘.
主要成果:
- STING激活诱导了Golgi衍生的囊泡,导致ATG16L1和V-ATPase依赖的自.
- 刺激性诱导的自激活了MiT/TFE转录因子.
- 脂质GABARAPs抑制了mTORC1,促进了MiT/TFE脱酸化和核转位.
- 通过GABARAP脂化激活LLRRK2的SING诱导的自.
- 自诱导ALIX介导的ESCRT招募,以保持内分泌体稳定性.
结论:
- 刺痛诱导的非正规性自在内分泌体平衡中发挥着多方面的作用.
- 该途径调节MiT/TFE转录因子和LRRK2活动.
- 研究结果揭示了将先天免疫,自和细胞平衡联系起来的新机制.
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