ER-phagy受体:选择性ER降解和疾病影响中的结构机制
Wen-Jing Yang1, Rui Sheng2,3
1Department of Pharmacology and Laboratory of Aging and Nervous Diseases, Jiangsu Key Laboratory of Drug Discovery and Translational Research for Brain Diseases, College of Pharmaceutical Sciences, Soochow University, Suzhou, 215123, China.
Acta pharmacologica Sinica
|January 27, 2026
概括
细胞内膜网膜 (ER) 稳态是由ER-phagy维持的,这是一种涉及特定受体的过程. 这些ER-phagy受体的功能障碍与各种疾病有关,提供治疗点.
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:
- 细胞内膜网膜 (ER) 对于蛋白质合成,折叠,脂质代谢和信号传递至关重要.
- ER 稳态是通过 ER-phagy (网膜),一种选择性的自过程降解 ER 组件来维持的.
- ER-phagy通过宏观ER-phagy,微型ER-phagy和ER-to-lysosome相关降解 (ERLAD) 发生.
研究的目的:
- 审查关于ER-phagy受体的当前知识.
- 总结新出现的证据,将ER-phagy功能障碍与疾病联系起来.
- 要突出ER-phagy受体的新型非降解功能.
主要方法:
- 关于ER-phagy研究的文献综述.
- 对ER-phagy受体 (例如FAM134A,TEX264,SEC62,RTN3L,CCPG1,ATL3) 的研究的分析.
- 检查将ER-phagy与疾病病理联系在一起的证据.
主要成果:
- 已经确定了10多个ER-phagy受体,进步了对ER质量控制的理解.
- ER-phagy功能障碍与神经系统,癌症,代谢,心血管,传染病和免疫系统疾病有关.
- ER-phagy受体可以形成ER-管状体 (ER-TBs),调解非传统的蛋白质分泌.
结论:
- ER-phagy受体在ER质量控制和细胞平衡中起着至关重要的作用.
- 准ER-phagy受体为相关疾病提供了潜在的治疗策略.
- 在ER质量控制之外,ER-phagy受体具有非降解性功能,例如调解蛋白质分泌.
相关概念视频
02:58Regulated Protein Degradation
8.8K
It is vital to regulate the activity of enzymatic as well as non-enzymatic proteins inside the cell. This can be achieved either through creating a balance between their rate of synthesis and degradation or regulating the intrinsic activity of the protein. Both these regulation mechanisms play an essential role in the normal functioning of cells.
Protein degradation plays two important roles in the cells. It helps to protect cells from misfolded or damaged proteins before they lead to a...
Protein degradation plays two important roles in the cells. It helps to protect cells from misfolded or damaged proteins before they lead to a...
8.8K
01:31Transducer Mechanism: Nuclear Receptors
2.5K
Nuclear receptors, or NRs, are unique transcription factors that regulate gene transcription and affect the cellular pathways involved in reproduction, development, or metabolism. Their ability to be stimulated by small lipophilic ligands and control vital cellular processes makes them ideal drug targets. Nearly 10-15% of currently prescribed drugs target these receptors.
About 48 different soluble family members of nuclear receptors are identified that can be divided into two main classes:
About 48 different soluble family members of nuclear receptors are identified that can be divided into two main classes:
2.5K
02:11Proteins: From Genes to Degradation
14.5K
Within a biological system, the DNA encodes the RNA, and the nucleotide sequence in the RNA further defines the amino acid sequence in the protein. This is referred to as “The Central Dogma of Molecular Biology” - a term coined by Francis Crick. Central dogma is a firm principle in biology that defines the flow of genetic information within any life form. The two fundamental steps in central dogma are - transcription and translation.
Transcription is the synthesis of RNA...
Transcription is the synthesis of RNA...
14.5K
01:03Olfactory Receptors: Location and Structure
11.7K
The process of olfaction, also known as the sense of smell, is a sophisticated chemical response system. The specialized sensory neurons that facilitate this process, known as olfactory receptor neurons, are situated in an upper segment of the nasal cavity, known as the olfactory epithelium. Olfactory sensory neurons are bipolar, with their dendrites extending from the epithelium's apex into the mucus that lines the nasal cavity. Airborne molecules, when inhaled, traverse the olfactory...
11.7K
01:30Transducer Mechanism: G Protein–Coupled Receptors
4.1K
G Protein–Coupled Receptors (GPCRs) are membrane-bound receptors that transiently associate with heterotrimeric G proteins and induce an appropriate response to various stimuli. GPCRs regulate critical physiological pathways and are excellent drug targets for treating diseases such as diabetes, cancer, obesity, depression, or Alzheimer's. Nearly 35% of approved drugs implement their therapeutic effects by selectively interacting with specific GPCRs.
GPCRs are also called heptahelical,...
GPCRs are also called heptahelical,...
4.1K
01:27Transducer Mechanism: Enzyme-Linked Receptors
4.0K
Enzyme-linked receptors are cell-surface receptors acting as an enzyme or associating with an enzyme intracellularly. They make excellent drug targets. Drugs can bind to the extracellular ligand-binding domain or directly affect their enzymatic domain and alter their activity.
Major types that are helpful drug targets include:
Major types that are helpful drug targets include:
4.0K