相关实验视频
Updated: Jun 24, 2025

09:22
In Vitro Aggregation Assays Using Hyperphosphorylated Tau Protein
Published on: January 2, 2015
18.4K
VCP通过特定的辅因子调节早期tau种子放大
Sushobhna Batra1, Jaime Iii Vaquer-Alicea1, Clarissa Valdez1
1UT Southwestern: The University of Texas Southwestern Medical Center.
Research square
|June 3, 2024
概括
含有瓦洛辛的蛋白质 (VCP) 控制神经退行性疾病中病态的快速播种. 在聚和细胞吸收的早期阶段,VCP及其辅助因子起着至关重要的作用.
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
- 生物化学 生物化学
背景情况:
- 神经退行性病症通过病理性组合的模板播种而进展.
- 聚合物的细胞间传播在几个小时内迅速发生,这表明细胞机械控制了这种急性阶段.
- 控制早期陶氏种植的特定参与者和机制在很大程度上是未知的.
研究的目的:
- 通过使用近距离标记来识别涉及种植急性阶段的细胞因素.
- 阐明瓦洛辛含蛋白 (VCP/p97) 在细胞内种和聚合中的作用.
主要方法:
- 靠近标签与分离-APEX2融合到tau重复域 (RD) 以识别在tau种子暴露后5小时内相互作用的蛋白质.
- 利用不朽的细胞系和初级人类神经元来研究VCP对种植的影响.
- 通过将细胞暴露在tau纤维或大脑同质体中,并通过基因和化学方法操纵VCP活动来研究tau种植.
主要成果:
- VCP的淘汰措施显著降低了tau的播种效率.
- 化学抑制剂的VCP显示对抗的效果在tau播种,与ML-240增加和NMS-873减少播种,只有在暴露后8小时内有效.
- 对VCP辅助因子的选显示,减少ATXN3,NSFL1C,UBE4B,NGLY1,OTUB1和NPLOC4减少了tau播种,而减少FAF2则增加了tau播种.
结论:
- 在播种的急性阶段,VCP起着关键的调节作用.
- VCP 抑制剂和协因子调制的不同效应表明,VCP 是细胞质复合体的一部分,该复合体将tau 种子指向降解或放大.
- 这些发现凸显了VCP作为病的潜在治疗点.
相关概念视频
cAMP-dependent Protein Kinase Pathways
6.3K
Cyclic Adenosine Monophosphate (cAMP) is an essential second messenger that activates protein kinase A (PKA) and regulates various biological processes. A single epinephrine molecule binds to GPCR and activates several heterotrimeric G proteins, each stimulating multiple adenylyl cyclase, amplifying the signal, and synthesizing large numbers of cAMP molecules. Small changes in cAMP concentration affect PKA activity. The binding of four cAMP molecules induces a conformational change in PKA,...
6.3K
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
Calmodulin-dependent Signaling
5.1K
Calmodulin (CaM) is a calcium-binding protein in eukaryotes that controls various calcium-regulated cellular processes. It has four calcium-binding sites that bind calcium to form the calcium-calmodulin ( Ca2+-CaM) complex. GPCR stimulation increases the calcium levels in the cells that bind to CaM and induces a conformational change.
The Ca2+-CaM complex does not have enzymatic activity by itself. Instead, the complex binds downstream target proteins, including membrane proteins or enzymes,...
The Ca2+-CaM complex does not have enzymatic activity by itself. Instead, the complex binds downstream target proteins, including membrane proteins or enzymes,...
5.1K
Anaphase Promoting Complex
2.8K
The stepwise destruction of specific proteins is necessary for the progression and completion of the cell cycle. Such proteins are ubiquitinated by ubiquitin ligases and then subsequently destroyed by the proteasome. The SCF (Skp1/Cullin/F-box) and the anaphase-promoting complex (APC) are two important ubiquitin ligases involved in cell cycle progression. While SCF is active throughout the cell cycle, APC gets activated during metaphase to anaphase transition. Cdc20 or Cdh1 binds to APC and...
2.8K
Microtubule Associated Proteins (MAPs)
4.3K
Microtubule function and architecture are regulated by an array of specialized proteins called microtubule-associated proteins or MAPs. These proteins are widespread across different organisms and have conserved protein motifs, like the multi-TOG domain for tubulin binding found in the CLASP family of MAPs. Some MAPs are lineage-specific based on their conserved domains. Their functions depend upon the cytoskeletal architecture and cell type they are located within. In-plant cells, a specific...
4.3K
GTPases and their Regulation
8.3K
Guanine nucleotide-binding proteins (G-proteins), also known as GTPases, are a superfamily of proteins that regulate many cellular processes, such as cell signaling, vesicular transport, and the regulation of cell shape and motility. Mutation or dysfunction of these proteins can lead to disease. There are around 40,000 known G-proteins that can broadly be classified into two groups ‒ small G-proteins consisting of a single domain and large multi-domain G-proteins.
Large G-proteins,...
Large G-proteins,...
8.3K

