在急性ER应力时,TMX4驱动的LINC复杂拆解和核外的不对称自
Marika K Kucińska1,2, Juliette Fedry3, Carmela Galli1
1Università della Svizzera italiana (USI), Faculty of Biomedical Sciences, Institute for Research in Biomedicine, CH-6500, Bellinzona, Switzerland.
Nature communications
|June 13, 2023
概括
哺乳动物细胞利用微ONM-phagy恢复核外结构后内网膜压力. 这个过程涉及特定的自途径来管理细胞平衡恢复期间的核包膜变化.
科学领域:
- 细胞生物学 细胞生物学
- 分子生物学分子生物学
- 有机体动力学 有机体动力学
背景情况:
- 细胞内膜网膜 (ER) 对于蛋白质和脂质合成至关重要,其体积和活性由细胞应激反应 (如未折叠蛋白质反应 (UPR) 和ER-phagy) 动态调节.
- 核外 (NE),一个专门的ER域,包括内外核膜 (INM和ONM),保护细胞的基因组.
研究的目的:
- 研究核膜在恒温性扰动期间适应并从ER扩张中恢复的机制.
- 阐明特定蛋白质和自途径在维持核外完整性方面的作用.
主要方法:
- 研究了ER扩张对哺乳动物细胞核外结构和动态的影响.
- 利用技术来分析LINC复合体的分解和外核膜膨胀.
- 标志着NE的非对称自,包括LC3脂化,SEC62和内分泌体通路.
主要成果:
- ER扩张触发了LINC复合体的TMX4减少酶依赖分解,导致外部核膜膨胀.
- 解决ER压力启动NE的不对称自,称为微ONM-phagy.
- 这一途径涉及SEC62和通过LAMP1/RAB7阳性内分泌体捕获ONM衍生的囊泡.
结论:
- 微ONM-phagy是一种用于NE重塑和恢复核外结构的新代谢途径.
- 这一过程对于在ER压力后维持细胞平衡至关重要.
- 这项研究揭示了一种新的器官质量控制机制,涉及核外的专门自.
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