SIGMAR1/Sigma-1受体:在稳定和翻译LC3BmRNA的关键调节者,用于自细胞形成
Yu-Jie Chen1, Jeffrey Knupp1,2, Emily Wang1
1Department of Cell & Developmental Biology, University of Michigan Medical School, Ann Arbor, MI, USA.
Autophagy
|October 6, 2024
概括
西格玛非阿片类细胞内受体1 (SIGMAR1) 通过稳定内网膜中的Atg8家族蛋白mRNA来调节自,促进高效的自细胞形成. 这一发现为神经退行性疾病提供了潜在的治疗策略.
科学领域:
- 细胞生物学 细胞生物学
- 分子生物学分子生物学
- 神经科学是一个神经科学.
背景情况:
- 宏自/自是一种通过溶酶体降解和回收组分的基本细胞过程,对于维持恒常状态至关重要.
- 细胞内膜网膜 (ER) 越来越多地被认为是其调节自的作用.
- Atg8家族蛋白质对于自细胞形成至关重要,这是自的一个关键步骤.
研究的目的:
- 确定Atg8家族蛋白质生物合成和脂化的新型调节剂.
- 阐明SIGMAR1 (西格玛非阿片类细胞内受体1) 在自途径中的特定作用.
- 探索SIGMAR1在与自有关的疾病中的治疗潜力.
主要方法:
- 单分子光 in situ 杂交 (smFISH) 以可视化mRNA局部化和翻译.
- 同免疫沉测试以确定SIGMAR1和mRNA之间的直接相互作用.
- 在有或没有SIGMAR的细胞中分析Atg8家族蛋白质水平和自流量1.1.
主要成果:
- 鉴定出SIGMAR1是Atg8蛋白家族mRNA生物合成和脂化的一个关键调节剂.
- SIGMAR1直接与MAP1LC3B/LC3B mRNA的3' UTR结合,使其稳定并促进ER的局部翻译.
- 缺少SIGMAR1导致Atg8家族蛋白水平降低,自流失,自细胞形成缺陷.
- SIGMAR1通过在ER的局部Atg8翻译促进了高效的自细胞形成.
结论:
- SIGMAR1在自中发挥着至关重要的作用,它通过调节ER的Atg8家族蛋白的局部翻译,这对于高效的自细胞生物生成至关重要.
- 这种机制与涉及招募先前存在的细胞质Atg8蛋白质的模型形成鲜明对比.
- 针对可药物治疗的SIGMAR1为与自功能受损相关的神经退行性疾病提供了一个有前途的治疗途径.
相关概念视频
Regulation of Nuclear Protein Sorting
2.4K
Nuclear protein sorting regulates nucleus composition and gene expression, crucial for determining the fate of a eukaryotic cell. Hence, the entry and exit of molecules across the nuclear envelope is a tightly controlled process. Nuclear protein sorting can be inhibited by one of the following ways: 1) masking cargo signal sequences, 2) modifying the nuclear receptor's affinity for cargo, 3) controlling the nuclear pore size, 4) retaining the cargo during its transit to the cytosol or the...
2.4K
Delivery Pathways to the Lysosome
6.2K
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...
6.2K
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
Formation of Lipopolysaccharides
1
Lipopolysaccharides (LPS) are crucial components of the outer membrane of Gram-negative bacteria, serving both structural and functional roles. It contributes to membrane stability and protects bacteria from host immune responses. LPS is composed of three major regions—lipid A, a core oligosaccharide, and an O antigen. The biosynthesis and assembly of LPS involve a highly coordinated set of enzymatic reactions and transport mechanisms. Additionally, LPS is recognized as an endotoxin,...
1
Translational Regulation
5
Translational regulation in prokaryotes ensures efficient protein synthesis by controlling ribosome access to mRNA. This regulation is mediated by secondary RNA structures, including translational riboswitches, RNA thermometers, and small RNAs (sRNAs), which respond to intracellular and environmental signals to modulate gene expression.Translational RiboswitchesRiboswitches in the leader region of mRNAs can regulate translation by altering the accessibility of the Shine-Dalgarno (SD) sequence,...
5
Directing Proteins to the Rough Endoplasmic Reticulum
7.2K
The organelle-specific signaling sequences direct proteins synthesized in the cytosol to their final destination like ER, mitochondria, peroxisomes, etc. Some of the proteins directed to ER are then trafficked via vesicles to other organelles within the cell or the extracellular environment through the Golgi complex. For example, the rough ER synthesizes soluble proteins for transportation to the lysosomes or secretion out of the cell. It can also synthesize transmembrane proteins that can...
7.2K


