SMURF1控制PPP3/氨酸复合体和TFEB在lysosomal生物发生的调节节点
Qin Xia1, Hanfei Zheng1, Yang Li1
1Key Laboratory of Molecular Medicine and Biological Diagnosis and Treatment (Ministry of Industry and Information Technology), School of Life Science, Beijing Institute of Technology, Beijing, China.
Autophagy
|November 1, 2023
概括
自调节器SMURF1通过促进TFEB核进口来控制 lysosomal生物发生. SMURF1桥接内膜损伤信号,激活PPP3/氨酸-TFEB通路进行细胞修复.
科学领域:
- 细胞生物学 细胞生物学
- 分子生物学分子生物学
- 自学研究 自学研究
背景情况:
- 宏自/自对于细胞平衡至关重要,涉及依赖于溶酶体的循环.
- 转录因子EB (TFEB) 的核转位通过饥饿诱导的MTOR失活和PPP3/氨酸激活来促进.
- 连接内膜损伤与PPP3/氨酸激活和自的机制尚不清楚.
研究的目的:
- 阐明自调节器SMURF1在控制TFEB核进口和溶酶体生物发生中的作用.
- 确定内膜损伤信号如何传输以激活PPP3/氨酸-TFEB通路.
主要方法:
- 研究了SMURF1抑制对溶酶体生物发生和TFEB转位的影响.
- 检查了 galectins,SMURF1 和PPP3/calcineurin在对 lysosomal损伤的反应中的相互作用.
- 在SMURF1调制下评估了TFEB核进口和PPP3/calcineurin活动.
主要成果:
- 阻断SMURF1影响了溶酶体生物发生和溶酶体损伤后的TFEB核转位.
- 盖莱克识别了内溶体损伤,将SMURF1和PPP3/氨酸招募到溶体中.
- SMURF1与LGALS3和PPP3CB形成一个复合体,稳定TFEB并激活 lysosomal生物发生.
- SMURF1对于LLOMe诱导的TFEB核导入 (在MTORC1抑制下) 和PPP3/calcineurin活性至关重要,通过分离PPP3CB的自身抑制域.
结论:
- SMURF1 作为环境压力和自机制之间的关键纽带.
- 与LGALS3和PPP3CB复合的SMURF1控制着溶酶体生物发生的TFEB激活.
- SMURF1积极调节PPP3/氨酸酸酶活性,增强TFEB介导的转录反应.
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