细胞质FKBPL和ER居民CKAP4共同调节ER-phagy和蛋白质分泌
Cathena Meiling Li1, Jaemin Kang1, Jongyeon Baek1
1School of Biological Sciences, Seoul National University, Gwanak-gu, Seoul, Korea.
Nature communications
|September 9, 2024
概括
一种新发现的蛋白质,FKBPL,充当了内分泌网膜 (ER) 调节器. 与CKAP4一起的FKBPL触发了ER碎片化和ER-phagy,影响了细胞平衡.
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:
- 细胞内膜网膜 (ER) 质量控制对于细胞平衡和应激适应至关重要.
- 细胞质和ER居住因子在ER分裂和ER-phagy中的作用仍然不完全理解.
研究的目的:
- 为了确定ER碎片化和ER-phagy的新型调节者.
- 阐明通过细胞系因子调节ER-phagy的分子机制.
主要方法:
- 进行了基于表型的功能获取屏幕,以确定ER-phagy调节器.
- 使用共免疫沉和寡合化试验研究了蛋白质与蛋白质相互作用.
- 分析了包括ER分裂,戈尔吉结构,溶酶体功能和蛋白质分泌在内的细胞表型.
主要成果:
- 鉴定了FKBPL,一种细胞质蛋白质,作为一种新型ER-phagy调节剂,在过度表达时诱导ER碎片化和ER-phagy.
- FKBPL充当了一个支架,连接CKAP4和与自相关的蛋白质 (LC3 / GABARAPs),CKAP4将FKBPL连接到ER-phagy货物.
- 诱导ER-phagy增强了FKBPL-CKAP4相互作用和ER的FKBPL寡合化.
- 由于FKBPL-CKAP4缺乏,导致戈尔吉分解,溶酶体损伤,增加ER衍生的分泌囊泡,并通过微小囊泡增强细胞质蛋白质分泌.
结论:
- 由CKAP4促进的FKBPL在诱导ER碎片化和ER-phagy方面发挥着至关重要的作用.
- FKBPL-CKAP4复合体通过调节ER循环和蛋白质分泌途径来调节细胞平衡.
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