RTN3L和CALCOCO1并行运行,以维持内 плазма网膜中的蛋白质稳定
Kamal Kumar1, Ravi Chidambaram1, Smriti Parashar1
1Department of Cellular and Molecular Medicine, University of California at San Diego, La Jolla, CA, USA.
Autophagy
|May 31, 2024
概括
三种受体,RTN3L,ATL3和CALCOCO1,通过网膜,维持内细胞网膜 (ER) 蛋白质稳定. RTN3L和ATL3对于ER-网膜位 (ERPHS) 的形成至关重要,而CALCOCO1则具有并行作用.
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:
- 网膜,一种选择性的自形式,对于维持内质网膜 (ER) 蛋白质稳定至关重要.
- 自受体在ER管道或平板板中起作用,RTN3L,ATL3和CALCOCO1被确定为ER管道中的关键介质.
- RTN3L通过将错误折叠的蛋白质向ER管内的ER-网膜位 (ERPHS) 来维持蛋白质静止.
研究的目的:
- 研究ATL3和CALCOCO1在蛋白质稳定中的作用及其与RTN3L的关系.
- 确定ATL3和CALCOCO1是否针对与RTN3L类似的错误折叠蛋白质货物.
- 阐明这些受体对ER蛋白质稳定有所贡献的机制.
主要方法:
- 对三种错误折叠,致病RTN3L基质的分析.
- 局部化研究以评估受体相互作用.
- 敲击实验以确定每个受体对ERPHS形成的必要性.
主要成果:
- 发现ATL3和CALCOCO1的目标是与RTN3L相同的自货物.
- 无论是RTN3L还是ATL3,都对RTN3L含有ERPHS的形成至关重要.
- 对于ERPHS的形成,CALCOCO1并不需要,这表明它具有不同的但并行的作用.
结论:
- RTN3L,ATL3和CALCOCO1在平行途径上运行,以维持ER蛋白质稳定.
- RTN3L和ATL3合作形成针对性蛋白质降解的ERPHS.
- 卡尔科科1通过独立于ERPHS形成的机制对蛋白质静止产生贡献.
相关概念视频
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
01:27Post-translational Translocation of Proteins to the RER
5.7K
A sizable fraction of proteins destined for ER are first synthesized in the cell cytosol and then transported across the ER membrane–a process called post-translational translocation. Similar to cotranslationally translocated proteins, these proteins also use the Sec translocon complex to enter the ER lumen.
Targeting proteins to the ER
Hsp40 and Hsp70 chaperone molecules bind the translated proteins in the cytosol to prevent their folding. The chaperone binding helps to keep the signal...
Targeting proteins to the ER
Hsp40 and Hsp70 chaperone molecules bind the translated proteins in the cytosol to prevent their folding. The chaperone binding helps to keep the signal...
5.7K
01:32Export of Misfolded Proteins out of the ER
3.6K
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...
3.6K
01:37The Unfolded Protein Response
4.5K
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...
4.5K
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
01:17Role of ER in the Secretory Pathway
5.4K
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...
5.4K