达利对DPP的扩散或内部化并不重要,而是通过对抗Tkv介导的DPP内部化,对DPP的稳定性至关重要
Niklas Simon1, Abu Safyan2,3,4,5,6, George Pyrowolakis3,4,5,6
1Growth & Development, Biozentrum, Spitalstrasse, University of Basel, Basel, Switzerland.
eLife
|January 24, 2024
概括
异常延迟的分裂 (Dally) 对Drosophila翅膀盘的发育至关重要. 它的核心蛋白与DPP相互作用,而它的肝硫酸盐链通过防止细胞内化来稳定DPP.
科学领域:
- 发展生物学 发展生物学
- 分子生物学分子生物学
- 细胞生物学 细胞生物学
背景情况:
- 肝酸硫酸蛋白质甘 (HSPGs) 是关键的细胞表面分子,调节形态原梯度的形成和信号传递.
- 在Drosophila翅膀盘中,Glypicans异常延迟的 (Dally) 和类似Dally的 (Dlp) 被认为可以通过它们的肝酸盐 (HS) 链冗余地控制Dpp形态变态梯度.
- 之前的模型建议glypicans促进或阻碍DPP传播,稳定DPP或回收DPP,但不同的HSPG功能仍然不清楚.
研究的目的:
- 阐明Dally和DLP在控制Dpp形态变态梯度形成和Drosophila翅膀盘中的信号传递中的不同作用.
- 为了研究达利的核心蛋白和HS链对DPP梯度调节的特定贡献.
主要方法:
- 为Drosophila中的Dally和Dlp生成基因组工程平台.
- 在DPP梯度形成和信号中分析Dally和DLP函数.
- 对Dally-Dpp和Dally HS-Dpp相互作用的研究.
主要成果:
- 只有Dally,而不是Dlp,被发现对Dpp梯度形成和信号发送至关重要.
- 达利的核心蛋白与DPP相互作用,但这种相互作用本身不足以发挥作用.
- 达利的HS链对于DPP梯度形成和信号传递至关重要,主要是通过稳定DPP在细胞表面.
- 达利的HS链对抗受体介导的DPP内部化,而不是促进DPP传播或回收.
结论:
- 达利在Drosophila翅膀盘中的Dpp形态基因梯度控制中发挥着关键的,非冗余的作用.
- 达利通过涉及其核心蛋白质和HS链的双重机制调节DPP信号.
- 达利的HS链通过抑制其内部化来稳定Dpp,为形态原梯度调节提供了一种新的机制.
关键词:
D. melanogaster. D. melanogaster. D. melanogaster. D. melanogaster. D. melanogaster. D. melanogaster. D. melanogaster. D. melanogaster. D. melanogaster. D. melanogaster. D. melanogaster. D. melanogaster. D. melanogaster. D. melanogaster. D. melanogaster. D. melanogaster. melanogaster. D. melanogaster. melanogaster. D. melanogaster. D. melanogaster. melanogaster. D.达利·达利 (Dally Dally) 是一个名为达利·达利 (Dally Dally) 的名人.在DPP/BMP中使用.细胞生物学 细胞生物学发育生物学是发展生物学.格莱皮卡纳 (Glypican) 是一种葡萄糖.形态原体是一种形态原体.机翼盘 机翼盘 机翼盘 机翼盘相关概念视频
Drugs that Stabilize Microtubules
2.0K
Microtubules are dynamic structures that undergo cycles of catastrophe and rescue. The microtubules play a central role in cell division by forming the spindle apparatus for segregating the chromosomes. This makes them ideal targets for regulating dividing cells in tumors and malignant cancer cells. Microtubule stabilizing drugs help stabilize the microtubule formation and promote its polymerization. Paclitaxel was the first microtubule stabilizing agent used as anticancer drug in chemotherapy...
2.0K
Dipeptidyl Peptidase 4 Inhibitors
187
Dipeptidyl peptidase 4 (DPP-4) is a serine protease widely distributed in the body. It's involved in the inactivation of GLP-1 and GIP hormones, which are crucial for insulin regulation. DPP-4 inhibitors, such as sitagliptin (Januvia), saxagliptin (Onglyza), linagliptin (Tradjenta), alogliptin (Nesina), and vildagliptin (Galvus), help increase the proportion of active GLP-1, enhancing insulin secretion. These inhibitors work by competitively binding to DPP-4. This binding causes a...
187
Inhibition of Cdk Activity
4.8K
The orderly progression of the cell cycle depends on the activation of Cdk protein by binding to its cyclin partner. However, the cell cycle must be restricted when undergoing abnormal changes. Most cancers correlate to the deregulated cell cycle, and since Cdks are a central component of the cell cycle, Cdk inhibitors are extensively studied to develop anticancer agents. For instance, cyclin D associates with several Cdks, such as Cdk 4/6, to form an active complex. The cyclin D-Cdk4/6 complex...
4.8K
Drug Distribution: Volume of Distribution
5.1K
The volume of distribution refers to the theoretical volume necessary to contain the entire amount of an administered drug at the same concentration observed in the blood plasma. The body's intracellular fluid compartment, which makes up two-thirds of the total body water, is contrasted with the extracellular fluid compartment—comprising plasma and interstitial fluid—that accounts for one-third. The volume of distribution can vary depending on the characteristics of the drug.
5.1K
Destabilization of Microtubules
2.7K
The destabilization of microtubules can occur during different stages of the microtubule lifecycle, such as nucleation or elongation. It can take place at either end of the microtubule or in the microtubule lattices as a whole. The lifespan of individual microtubules within a cell varies according to the cell type and stage of the cell cycle. During interphase, the lifespan of the microtubule is about 30 minutes, while during cell division, it is about 15 minutes. In axonal microtubules of...
2.7K
IP3/DAG Signaling Pathway
12.1K
Membrane lipids such as phosphatidylinositol (PI) are precursors for several membrane-bound and soluble second messengers. Specific kinases phosphorylate PI and produce phosphorylated inositol phospholipids. One such inositol phospholipids are the phosphatidylinositol-4,5 bisphosphate [PI(4,5)P2], present in the inner half of the lipid bilayer. Upon ligand binding, GPCR stimulates Gq proteins to turn on phospholipase Cꞵ. Activated phospholipase Cꞵ cleaves PI(4,5)P2 and...
12.1K


