由V-ATPase-ATG16L1-LC3C轴介导的网膜食
1Key Laboratory of Biomacromolecules (CAS), National Laboratory of Biomacromolecules, CAS Center for Excellence in Biomacromolecules, Institute of Biophysics, Chinese Academy of Sciences, Beijing, China.
Autophagy
|February 13, 2024
概括
错误折叠的α-1抗素 (Z-AAT) 在ER退出部位触发了一种独特的内分泌网膜 (ER) 降解形式. 这种称为网球的过程,通过清除受损的ER组件,有助于维持蛋白质质量控制.
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:
- 网膜化,内细胞网膜 (ER) 的 lysosomal 降解,对于细胞蛋白质质量控制和有机体稳定至关重要.
- ER 出口点 (ERES) 是从 ER 到戈尔吉装置的蛋白质运输的关键结点.
研究的目的:
- 为了阐明一个非正规的网膜食路径的机制.
- 调查错误折叠的α-1抗素 (Z-AAT) 在诱导ERESs的ER降解中的作用.
- 为了确定参与这种特定的网膜食过程的分子参与者.
主要方法:
- 在细胞中诱导Z-AAT突变表达.
- 免疫光显微镜可视化蛋白质定位和有机体动力学.
- 生物化学测试评估ER-to-Golgi运输封锁. 生物化学测试评估ER-to-Golgi运输封锁. 生物化学测试用于评估ER-to-Golgi运输封锁.
- 基因操纵用于研究V-ATPase,ATG16L1,LC3C和RETREG1/FAM134B-2的功能.
主要成果:
- 错误折叠的Z-AAT积累并阻碍了ER到Golgi的运输.
- V-ATPase和ATG16L1被招募到ERES中,通过LC3C装饰进行中介.
- 脂化LC3C招募受体RETREG1/FAM134B-2,以启动网球.
- "ER出口封锁"作为一个一般信号,激活了这种V-ATPase-ATG16L1-LC3C介导的网膜轴.
结论:
- ERES可以从出口转向降解途径,以管理错误折叠的蛋白质应激.
- V-ATPase-ATG16L1-LC3C-RETREG1/FAM134B-2轴代表了非正规网膜的新机制.
- 这一途径对于在特定压力条件下保持ER蛋白质质量控制至关重要.
相关概念视频
Recycling Endosomes and Transcytosis
2.7K
The recycling endosome, also known as the endosomal recycling compartment (ERC), is a part of the slow-recycling process of the endocytic pathway. Molecules internalized through receptor-mediated endocytosis are either degraded in the lysosomes or are recycled to the plasma membrane through the fast- or slow-recycling route.
The recycling endosome is not a single organelle but an extensively tubulated network of recycling pathways. It functions in storing molecules or transporting them across...
The recycling endosome is not a single organelle but an extensively tubulated network of recycling pathways. It functions in storing molecules or transporting them across...
2.7K
Export 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
Delivery Pathways to the Lysosome
6.5K
Eukaryotic cells use different mechanisms to eliminate toxic waste obsolete and worn-out substances. Lysosomes play a pivotal role in this, and hence, these substances are carried to the lysosome from other parts of the cell and extracellular space through different pathways. The most elaborately studied pathways to the lysosome are the endocytic pathways.
Endocytosis
In endocytosis, the cell membrane takes up macromolecules and particles from the surrounding medium. Clathrin-mediated...
Endocytosis
In endocytosis, the cell membrane takes up macromolecules and particles from the surrounding medium. Clathrin-mediated...
6.5K
Autophagy
4.2K
Autophagy is a self-digesting process by which a cell protects itself from threats both within and outside the cell, ranging from abnormal proteins to invading bacteria. In this process, obsolete components of the cell and invading microbes are degraded by hydrolytic enzymes active in an acidic environment of the lysosomal lumen.
An autophagic pathway consists of a series of signaling events activated in response to diverse stress and physiological conditions such as food deprivation,...
An autophagic pathway consists of a series of signaling events activated in response to diverse stress and physiological conditions such as food deprivation,...
4.2K
ER Retrieval Pathway
3.8K
In the secretory pathway, vesicles transport proteins from one cellular compartment to another in forward transport to deliver the protein to its correct location. Occasionally, misfolded proteins and incorrect proteins escape their original compartments, and a retrieval pathway is used to return the escaped proteins to their original compartment.
The ER uses many checkpoints to prevent the entry of incorrectly folded or a resident protein as cargo onto a transport vesicle. These mechanisms...
The ER uses many checkpoints to prevent the entry of incorrectly folded or a resident protein as cargo onto a transport vesicle. These mechanisms...
3.8K
Post-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


