细胞内膜网膜应激和展开的蛋白质反应在免疫细胞功能中的作用
Goshi Matsushima1, Yuhki Yanase1, Tadashi Nakagawa2
1Department of Clinical Pharmacology and Therapeutics, Graduate School of Biomedical and Health Sciences, Hiroshima University, Hiroshima, Japan.
Frontiers in immunology
|November 10, 2025
概括
细胞内膜网膜 (ER) 的压力和未折叠的蛋白质反应 (UPR) 调节免疫细胞的功能. 本综述详细介绍了ER压力如何影响各种免疫细胞,这对于理解炎症和开发疗法至关重要.
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:
- 细胞内膜网膜 (ER) 应激和展开的蛋白质反应 (UPR) 是免疫细胞功能和炎症的关键调节者.
- 涉及传感器 IRE1α,PERK 和 ATF6 的 UPR 维持恒温状态,但在失调时可以驱动疾病.
- 新出现的证据强调了UPR在免疫细胞命运,激活和细胞因子生产中的作用.
研究的目的:
- 提供ER压力和UPR对各种免疫细胞类型的影响的全面概述.
- 探索ER应激反应在免疫中的细胞类型特定和上下文依赖的功能.
- 强调了解这些机制对于有针对性的治疗开发的重要性.
主要方法:
- 文献综述综合了ER压力和免疫学中UPR的最新发现.
- 对研究UPR对免疫细胞子集的影响的研究分析.
- 整合关于外周和中央免疫系统组件的知识.
主要成果:
- ER压力和UPR显著影响免疫细胞功能,命运和炎症反应.
- UPR的调节失调有助于与免疫相关的病原发生.
- 在不同类型的免疫细胞中,ER应激的具体作用有所不同,包括单细胞,巨细胞,树突细胞,粒细胞,T细胞,B细胞,微质细胞和星体细胞.
结论:
- 了解ER压力和UPR在各种免疫细胞中的复杂作用至关重要.
- 调节ER压力路径的向疗法具有治疗炎症和免疫相关疾病的潜力.
- 需要进行进一步的研究,以充分阐明特定免疫细胞群中的上下文依赖的UPR功能.
相关概念视频
01:37The Unfolded Protein Response
6.2K
The ER is the hub of protein synthesis in a cell. It has robust systems to quality control protein folding and also for degradation of terminally misfolded proteins. Under normal conditions, a small proportion of misfolded proteins that cannot be salvaged need to be transported to the cytoplasm by the ER-associated degradation or ERAD pathways. However, if the ERAD cannot handle the misfolded proteins, the cell activates the unfolded protein response or UPR to adjust the protein folding...
6.2K
01:31Regulation of the Unfolded Protein Response
2.9K
Inositol-requiring kinase one or IRE1 is the most conserved eukaryotic unfolded protein response (UPR) receptor. It is a type I transmembrane protein kinase receptor with a distinctive site-specific RNase activity. As the binding mechanics of the misfolded proteins with the N-terminal domain of IRE-1 are unclear, three binding models — direct, indirect, and allosteric -- are proposed for receptor activation. Nevertheless, it is known that once a misfolded protein associates with IRE1, it...
2.9K
01:17Role of ER in the Secretory Pathway
6.9K
Eukaryotic cells have a special pathway that enables communication between various intracellular membrane-bound compartments and also with the extracellular environment. This pathway is termed as the secretory pathway.
Components of the secretory pathway
About a third of proteins synthesized in the cell are sorted via the secretory route. They shuffle between different compartments in membrane-bound vesicles until they reach their final destination. The main intracellular compartments involved...
Components of the secretory pathway
About a third of proteins synthesized in the cell are sorted via the secretory route. They shuffle between different compartments in membrane-bound vesicles until they reach their final destination. The main intracellular compartments involved...
6.9K
01:29Protein Folding Quality Check in the RER
5.0K
ER is the primary site for the maturation and folding of soluble and transmembrane secretory proteins. The calnexin cycle is a specific chaperone system that folds and assesses the confirmation of N-glycosylated proteins before they can exit the ER lumen. The primary players of this quality check pipeline are the lectins, ER-resident chaperones, and a glucosyl transferase enzyme. In case the calnexin system in the lumen fails to salvage a misfolded protein, it is transported to the cytoplasm...
5.0K
01:26Protein Modifications in the RER
6.8K
Modification of secretory and transmembrane proteins entering the rough ER begins in the ER lumen. These modifications aid in protein folding and stabilize the acquired tertiary structure. Protein modifications in the rough ER co-occur at different stages of protein folding.
Broadly, these modifications can be categorized into four main categories — glycosylation, formation of disulfide bonds, assembly of protein subunits, and specific proteolytic cleavages like removal of signal...
Broadly, these modifications can be categorized into four main categories — glycosylation, formation of disulfide bonds, assembly of protein subunits, and specific proteolytic cleavages like removal of signal...
6.8K
01:32Export of Misfolded Proteins out of the ER
5.0K
After folding, the ER assesses the quality of secretory and membrane proteins. The correctly folded proteins are cleared by the calnexin cycle for transport to their final destination, while misfolded proteins are held back in the ER lumen. The ER chaperones attempt to unfold and refold the misfolded proteins but sometimes fail to achieve the correct native conformation. Such terminally misfolded proteins are then exported to the cytosol by ER-associated degradation or ERAD pathway for...
5.0K