相关实验视频
Updated: Jun 29, 2025

10:34
A High-content Assay for Monitoring AMPA Receptor Trafficking
Published on: January 28, 2019
7.7K
陶调节神经元树突中的弧度稳定性,通过一种对蛋白质酶敏感但与无处不在素独立的途径
Dina W Yakout1, Ankit Shroff2, Wei Wei1
1Neuroscience Institute, Georgia State University, Atlanta, Georgia, USA.
The Journal of biological chemistry
|March 29, 2024
概括
在阿尔茨海默氏症 (AD) 中蛋白的积累降低了活性调节的细胞骨相关蛋白 (Arc) 的稳定性,影响了突触可塑性和记忆力. 这种tau-Arc相互作用对于理解AD的发病过程至关重要.
科学领域:
- 神经科学是一个神经科学.
- 细胞生物学 细胞生物学
- 分子生物学分子生物学
背景情况:
- 包括阿尔茨海默氏症 (AD) 在内的病症涉及总沉积.
- 调节突触可塑性,而Arc蛋白对于学习和记忆至关重要.
- 弧线与AD有关,并影响粉样β释放.
研究的目的:
- 在AD的背景下调查tau和Arc蛋白之间的关系.
- 阐明陶影响Arc稳定性和功能的分子机制.
- 确定在通过Arc.调节突触可塑性的作用.
主要方法:
- 对阿克蛋白水平与阿尔茨海默病状态和严重程度的分析.
- 在初级海马神经元和小鼠模型 (Tau KO小鼠) 中对tau水平的实验操纵.
- 研究对Arc稳定性,无处不在和与蛋白质酶的相互作用的影响.
- 评估Arc对GluA1受体局部化和突触功能的影响.
主要成果:
- 降低的弧度水平与阿尔茨海默病状态和疾病严重程度相关.
- 的过度表达以蛋白质酶依赖的方式降低了Arc的稳定性,而不依赖于无处不在.
- 陶积累导致GluA1受体表达和局部化在树突中发生变化.
- 对于P301L突变体,没有观察到这些效应,这表明涉及特定的形状.
结论:
- 在树突中积累的陶会通过降低弧度稳定性来损害突触功能.
- 陶在调节弧度稳定性和AMPA受体向方面发挥着生理作用.
- 这些发现为阿尔茨海默氏症中陶中介突触功能障碍提供了分子基础,并突出了Arc作为关键参与者.
相关概念视频
Regulated Protein Degradation
7.2K
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...
7.2K
The Proteasome
832
Eukaryotic cells can degrade proteins through several pathways. One of the most important among these is the ubiquitin-proteasome pathway. It helps the cell eliminate the misfolded, damaged, or unwarranted cytoplasmic proteins in a highly specific manner.
In this pathway, the target proteins are first tagged with small proteins called ubiquitin. This involves participation of a series of enzymes including— E1 (ubiquitin-activating enzyme), E2 (ubiquitin-conjugating enzyme), and E3...
In this pathway, the target proteins are first tagged with small proteins called ubiquitin. This involves participation of a series of enzymes including— E1 (ubiquitin-activating enzyme), E2 (ubiquitin-conjugating enzyme), and E3...
832
The Unfolded Protein Response
4.6K
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...
4.6K
Regulation 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
Covalently Linked Protein Regulators
6.8K
Proteins can undergo many types of post-translational modifications, often in response to changes in their environment. These modifications play an important role in the function and stability of these proteins. Covalently linked molecules include functional groups, such as methyl, acetyl, and phosphate groups, and also small proteins, such as ubiquitin. There are around 200 different types of covalent regulators that have been identified.
These groups modify specific amino acids in a protein....
These groups modify specific amino acids in a protein....
6.8K
The Proteasome Structure
749
The ubiquitin-proteasome pathway is a well-known mechanism utilized by eukaryotic cells to remove cytoplasmic proteins that are misfolded, damaged, or no longer needed. In this pathway, the protein that needs to be eliminated undergoes a process called ubiquitination, where a chain of ubiquitin molecules is attached to the 48th lysine residue of the target protein. This ubiquitin modification helps the proteasome distinguish between a target protein and a healthy protein.
The proteasome is an...
The proteasome is an...
749

