在CADHERIN-11和PDGFR路径之间存在多层交叉的计算证据
Zeynep Karagöz1, Fiona R Passanha1, Lars Robeerst1
1Department of Cell Biology-Inspired Tissue Engineering (cBITE), MERLN Institute for Technology-Inspired Regenerative Medicine, Maastricht University, P.O. Box 616, 6200 MD, Maastricht, The Netherlands.
Scientific reports
|September 22, 2023
概括
细胞表面受体,如cadherin-11和血小板衍生生长因子受体 (PDGFRs) 影响人类介质干细胞 (hMSC) 的增殖. 计算建模揭示了β-catenin和ERK抑制剂之间的下游交叉声,影响hMSC行为.
科学领域:
- 干细胞生物学 干细胞生物学
- 细胞信号传递 细胞信号传递
- 计算生物学是一种计算生物学.
背景情况:
- 细胞表面受体调节人间介质干细胞 (hMSC) 的分化和自我更新.
- 卡德林-11,II型经典卡德林,通过与其他受体的相互作用影响hMSC命运承诺.
- 血小板衍生生长因子受体 (PDGFRs) 是cadherin-11的假设相互作用伙伴,对PDGFR-α和PDGFR-β活性有不同的影响.
研究的目的:
- 在hMSCs中计算模拟cadherin-11和PDGFRs之间的相互作用.
- 研究由这些受体启动的信号通路之间的潜在下游交叉声.
- 预测受体交叉对hMSC增殖的影响.
主要方法:
- 开发一个计算模型,表示cadherin-11,PDGFR-α和PDGFR-β之间的实验验证相互作用.
- 模拟模型以模仿cadherin-11的敲击实验.
- 对下游信号活动的分析和对细胞增殖影响的预测.
主要成果:
- 卡德林-11 Knockdown 降低了 hMSC 增殖,与实验发现一致.
- 模型模拟显示了在受体水平上cadherin-11和PDGFRs之间的交叉声.
- 预测表明,一个新的下游交叉层涉及β-catenin和ERK抑制蛋白 (例如,DUSP1).
结论:
- 这项研究阐明了hMSCs中cadherin-11和PDGFR之间的多级交叉声.
- 确定了之前未知的β-catenin和ERK抑制剂之间的下游交叉通话机制.
- 这些发现增强了对细胞表面受体相互作用如何调节hMSC增殖的理解.
相关概念视频
Cadherins in Tissue Organization
3.0K
The cadherins are a superfamily of cell adhesion molecules comprising over 180 variants, with specific tissues expressing a particular combination of cadherin types. Cadherins generally exhibit homophilic binding; i.e., cadherins on one cell bind to cadherins of the same or closely related type on another cell. Thus, cells of the same type have a specific affinity to bind to each other and sort themselves into clusters to form tissues.
Cell Sorting During Development
Cell sorting plays an...
Cell Sorting During Development
Cell sorting plays an...
3.0K
Structure of Cadherins
3.4K
The cadherins were one of the first cell adhesion molecules discovered; the term “cadherins” is based on their calcium-dependent adhering properties. The first cadherins discovered on the epithelial, neuronal, and placental cells were named E-cadherin, P-cadherin, and N-cadherin, respectively. These classical cadherins share sequence and structural similarities. Other cadherins, including those involved in cell signaling, are grouped into non-classical cadherins. This...
3.4K
Notch Signaling Pathway
4.3K
The Notch signaling pathway is a major intracellular signaling pathway that is highly conserved over a broad spectrum of metazoan species. It stands unique from other intracellular signaling mechanisms in animals because notch protein itself acts as the receptor as well as the primary signaling molecule.
The Notch gene came into the limelight in 1914 after the discovery that its mutation in Drosophila melanogaster leads to a serrated (or "notched") wing margin phenotype. It was not...
The Notch gene came into the limelight in 1914 after the discovery that its mutation in Drosophila melanogaster leads to a serrated (or "notched") wing margin phenotype. It was not...
4.3K
Hedgehog Signaling Pathway
7.4K
The Hedgehog gene (Hh) was first discovered due to its control of the growth of disorganized, hair-like bristles phenotype in Drosophila, much like hedgehog spines. Hh plays a crucial role in the development of organs and the maintenance of homeostasis in both invertebrates and vertebrates. However, while Drosophila has only one Hh protein, mammals have multiple functional Hedgehog proteins - Sonic (Shh), Desert (Dhh), and Indian Hedgehog (Ihh). All of these homologous proteins have adapted to...
7.4K
Interactions Between Signaling Pathways
6.3K
Signaling cascades usually lack linearity. Multiple pathways interact and regulate one another, allowing cells to integrate and respond to diverse environmental stimuli.
Convergence and divergence, and cross-talk between signaling pathways
Two distinct signaling pathways can converge on a single functional unit, which may either be a single protein or a complex of proteins. The response is either functionally distinct or synergistic between the two pathways but different from the response...
Convergence and divergence, and cross-talk between signaling pathways
Two distinct signaling pathways can converge on a single functional unit, which may either be a single protein or a complex of proteins. The response is either functionally distinct or synergistic between the two pathways but different from the response...
6.3K
Role Of Notch Signalling In Intestinal Stem Cell Renewal
2.1K
Notch signaling was first discovered in Drosophila melanogaster, where it is involved in cell lineage differentiation. Notch signaling regulates the maintenance and differentiation of intestinal stem cells or ISCs by controlling the expression of atonal homolog 1 or Atoh1. Atoh1 directs cells to differentiate into secretory cells.
Direct cell-to-cell contact is needed for the activation of Notch signaling. The signal is initiated when a notch ligand binds to a receptor on an adjacent cell, also...
Direct cell-to-cell contact is needed for the activation of Notch signaling. The signal is initiated when a notch ligand binds to a receptor on an adjacent cell, also...
2.1K


