ER压力,未折叠的蛋白质反应和骨质细胞形成:一篇评论
Wangli Huang1, Yining Gong1, Liang Yan1
1Department of Spine Surgery, Honghui Hospital, Xi'an Jiaotong University, Xi'an 710054, China.
Biomolecules
|July 29, 2023
概括
展开的蛋白质反应 (UPR) 与骨质细胞形成和骨质再吸收有关. 特定的UPR通路促进骨质细胞形成,为骨质疏松症等骨疾病提供潜在的治疗点.
科学领域:
- 细胞生物学 细胞生物学
- 骨生物学 骨生物学 骨生物学
- 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) 是细胞的适应机制.
- 骨质细胞生成涉及显著的蛋白质合成,使其容易受到ER压力.
- 越来越多的证据将ER压力和UPR与骨质细胞活性和骨质再吸收联系起来.
研究的目的:
- 审查和讨论与骨质细胞形成有关的UPR信号级联.
- 探索UPR在骨再吸收中的作用.
- 确定涉及骨质细胞过分分化的疾病的潜在治疗点.
主要方法:
- 关于ER压力,UPR,骨质细胞生成和骨再吸收的研究的文献综述.
- 对UPR信号通路 (PERK,IRE1-XBP1,CREBH) 的分析及其下游影响.
- 检查UPR组件对骨质细胞分化和功能的影响.
主要成果:
- UPR信号 (PERK,CHOP,IRE1-XBP1) 通过对骨质母细胞中的RANKL进行上调来促进骨质母细胞发生.
- IRE1和PERK通路通过NF-κB,MAPK信号传递和促炎因素增强骨质细胞形成.
- 通过增加NFATc1表达,CREBH促进骨质细胞分化.
结论:
- UPR在骨质细胞形成和骨再吸收中发挥着重要作用.
- 特定的UPR通路调节骨质细胞分化和活动.
- 需要进一步的研究,以充分阐明UPR机制的潜在治疗应用在骨质疏松症等骨疾病.
相关概念视频
01:37The Unfolded Protein Response
4.7K
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...
4.7K
01:31Regulation of the Unfolded Protein Response
2.5K
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...
2.5K
01:17Role of ER in the Secretory Pathway
5.5K
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...
5.5K
01:29Protein Folding Quality Check in the RER
3.7K
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...
3.7K
01:32Export of Misfolded Proteins out of the ER
3.7K
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...
3.7K
01:26Protein Modifications in the RER
5.3K
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...
5.3K