展开的蛋白质反应在肠道生理学的基本作用
Claudio Hetz1,2,3,4, Juan Francisco Silva-Agüero2,3,4, Lisa M Ellerby1
1Buck Institute for Research on Aging, Novato, California, USA.
eGastroenterology
|February 13, 2025
概括
展开的蛋白质反应 (UPR) 对于肠道上皮质健康至关重要,可以控制内分泌网膜 (ER) 的压力. UPR和ER压力的失调有助于IBD和结肠癌等肠道疾病.
科学领域:
- 胃肠病学 胃肠病学
- 细胞生物学 细胞生物学
- 免疫学 免疫学 免疫学
背景情况:
- 肠上皮是调节宿主微生物群相互作用,营养吸收和全身新陈代谢的关键屏障.
- 皮质细胞面临着来自肠道光和高分泌需求的持续性蛋白质稳定挑战,需要积极展开的蛋白质反应 (UPR).
- 细胞内膜网膜 (ER) 应激和UPR对于肠上皮质平衡,粘液产生和宿主-微生物通信至关重要.
研究的目的:
- 审查最近的进展,将UPR和ER压力与肠道生理学联系起来.
- 探索UPR和ER应激在肠道疾病中的作用.
- 讨论ER压力和UPR在衰老和肠道疾病中的治疗策略.
主要方法:
- 对UPR和ER压力研究近期进展的文献综述.
- 分析特定ER应力传感器在肠道平衡中的作用.
- 检查UPR功能障碍与肠道炎症和瘤疾病之间的联系.
主要成果:
- UPR对于肠上皮细胞来说至关重要,以管理ER压力并维持功能.
- 特定的ER应激传感器,如需要异醇的跨膜激酶/内核酶β,在肠道平衡中发挥关键作用.
- 慢性ER压力或UPR媒介突变与炎症性肠病,性结肠炎和结肠癌有关.
结论:
- UPR和ER压力是肠道上皮功能和疾病发病的核心.
- 准ER压力和UPR通路为肠道疾病提供了潜在的治疗途径.
- 保持UPR功能对于肠道健康至关重要,特别是在衰老和肠道疾病期间.
更多相关视频
相关概念视频
01:31Regulation of the Unfolded Protein Response
2.4K
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...
2.4K
01:37The Unfolded Protein Response
4.4K
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...
4.4K
01:22Role of Ephrin-Eph Signalling in Intestinal Stem Cell Renewal
2.2K
Erythropoietin-producing hepatocellular carcinoma receptor (Eph) and its ligand, Eph receptor-interacting protein (Ephrin) were first discovered in the human carcinoma cell line, hence the name. Ephrin-Eph interaction guides cells to reach their appropriate location in adult tissues. They also play an essential role in the immune system by helping in immune cell migration, adhesion, and activation. Based on their structure and function, Eph is divided into two classes — EphA and EphB.
2.2K
01:12Role Of Notch Signalling In Intestinal Stem Cell Renewal
2.0K
Notch signaling was first discovered in Drosophila melanogaster, where it is involved in cell lineage differentiation. Notch signaling regulates the maintenance and differentiation of intestinal stem cells or ISCs by controlling the expression of atonal homolog 1 or Atoh1. Atoh1 directs cells to differentiate into secretory cells.
Direct cell-to-cell contact is needed for the activation of Notch signaling. The signal is initiated when a notch ligand binds to a receptor on an adjacent cell, also...
Direct cell-to-cell contact is needed for the activation of Notch signaling. The signal is initiated when a notch ligand binds to a receptor on an adjacent cell, also...
2.0K
01:17Role of ER in the Secretory Pathway
5.2K
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...
5.2K
01:23Renewal of Intestinal Stem Cells
2.5K
The intestinal epithelial lining rapidly renews every 4 to 5 days. The renewal is facilitated by intestinal stem cells (ISCs) located at the base of the crypt– a gland located at the bottom of each villus. ISCs divide asymmetrically to form new stem cells and progenitor daughter cells. The daughter cells are called transit-amplifying (TA) cells which move upwards along the crypt and either differentiate into absorptive cells– the enterocytes or secretory cells– including the...
2.5K