由ER-phagy受体塑造的管状ER结构参与压力诱导的戈尔吉绕道
Min Seok Song1, Hun Ju Sim2, Sung Ho Eun3
1Department of Pharmacology, Woo Choo Lee Institute for Precision Drug Development, Graduate School of Medical Science Brain Korea 21 Project, Yonsei University College of Medicine, Seoul 03722, Republic of Korea; Department of Physiology, Gyeongsang National University College of Medicine, Jinju 52727, Republic of Korea.
Developmental cell
|February 7, 2025
概括
细胞应激会通过ER管体 (ER-TB) 触发非传统的蛋白质分泌 (UPS). 这些结构,包括ATL3和RTN3L,在压力期间调解CFTR和SARS-CoV-2尖端蛋白等蛋白质的运输.
科学领域:
- 细胞生物学 细胞生物学
- 分子生物学分子生物学
- 病毒学 病毒学
背景情况:
- 细胞应激,特别是内等质网膜 (ER) 应激,诱导戈尔吉独立的非传统蛋白质分泌 (UPS).
- 控制这种压力诱导的UPS路径的分子机制尚不清楚.
- UPS对于各种细胞功能至关重要,并与疾病有关.
研究的目的:
- 阐明压力诱导的非传统蛋白质分泌 (UPS) 的分子机制.
- 研究ER相关结构在介导跨膜蛋白的UPS中的作用.
- 探索特定的ER-phagy受体在这个过程中的参与.
主要方法:
- 相对光和电子显微镜 (CLEM) 用于可视化细胞结构.
- 在HEK293和HeLa细胞中进行基因淘汰和补充实验.
- 对囊性纤维化转膜导电调节器 (CFTR) 和SARS-CoV-2尖端蛋白的蛋白质贩运的分析.
主要成果:
- 由ATL3和RTN3L形成的ER管体 (ER-TB) 在UPS促进条件下被诱导.
- 淘汰ATL3或RTN3可以抑制ER-TB的形成,并且可以抑制流通不足的CFTR的UPS.
- ATL3参与了SARS-CoV-2尖端蛋白贩运和卷曲的膜形成.
- 结合ATL3和RTN3L的表达促进了ER-TB的形成和UPS.
结论:
- ER管状体 (ER-TB) 是一种关键结构,可以调解压力诱导的非传统蛋白质分泌 (UPS).
- ATL3和RTN3L是ER-TB形成和随后蛋白质分泌的关键组成部分.
- 经ER-TB介导的UPS在贩运SARS-CoV-2尖端蛋白和CFTR等与疾病相关的蛋白质等病毒蛋白中发挥作用.
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