在集体细胞迁移中通过EGFR的E-cadherin依赖酸化来调节细胞间粘度
Chaoyu Fu1, Florian Dilasser1, Shao-Zhen Lin2
1Mechanobiology Institute, National University of Singapore, Singapore 117411, Singapore.
概括
依赖E-cadherin的上皮生长因子受体 (EGFR) 活性调节细胞间粘度,控制集体细胞迁移模式. 这种机制控制细胞运动模式,并保持迁移速度,而不会改变结点张力.
科学领域:
- 细胞生物学 细胞生物学
- 生物物理学的生物物理.
- 癌症研究 癌症研究
背景情况:
- 集体细胞迁移对于伤口愈合,发育和癌症转移至关重要.
- 附着结 (AJs) 调节细胞凝聚力和迁移,但actin皮质在结的可塑性和应力消散中的作用尚不清楚.
研究的目的:
- 为了研究actin皮质动力学如何影响集体细胞迁移期间的结节可塑性.
- 为了阐明在AJs.压力消散的机制.
- 了解细胞间粘度是如何调节的.
主要方法:
- 研究了连接体独立的上皮生长因子受体 (EGFR) 酸化在E-cadherin粘附的下游.
- 利用Rac路径来调节actin动力学.
- 开发并使用了具有可调节节点粘度的顶点模型.
主要成果:
- 确定了一个反循环,其中依赖E-cadherin的EGFR活性通过Rac调节的活性动态来控制细胞间粘度.
- 证明EGFR活性控制集体细胞迁移模式,独立于细胞间张力.
- 观察到有效粘度的调节,导致扩张单层中从旋转到层状流动模式的过渡.
结论:
- 以E-cadherin为媒介的EGFR信号提供了一个新的机制来调节集体细胞迁移模式.
- 由EGFR和actin动力学调节的细胞间粘度是协调细胞运动和迁移模式的关键因素.
- 提出的顶点模型准确地复制了观察到的细胞流现型,验证了可调节的结点粘度的重要性.
相关概念视频
01:13Cell-matrix's Response to Mechanical Forces
2.6K
In animal cells, the extracellular matrix allows cells within tissues to withstand external stresses and transmits signals from the outside of the cell to the inside. The extracellular matrix is extensive, and its composition varies between different types of tissues. For example, the reticular fibers and ground substance make up the ECM in loose connective tissue, while collagen and bone minerals make up the ECM of bone tissue.
Anchoring junctions mechanically attach a cell to the...
Anchoring junctions mechanically attach a cell to the...
2.6K
01:32Cytoskeletal Coordination in Cell Migration
4.7K
A migrating cell changes its shape during the cyclic events of attachment and detachment from the substratum and repositions the cell organelles correspondingly. These complex events are orchestrated by the dynamic cytoskeletal network comprising actin filaments, intermediate filaments, and microtubules. Cytoskeletal crosstalk — the direct and indirect communication between the different components — is crucial for this coordination. Direct communication involves various linker...
4.7K
01:24Regulation of Angiogenesis and Blood Supply
2.5K
Rapidly dividing tumors, embryos, and wounded tissues require more oxygen than usual, lowering the oxygen concentration in the blood. At low oxygen or hypoxic conditions, an oxygen-sensitive transcription factor called the hypoxia-inducible factor 1 or HIF1 is activated. HIF1 is a dimeric protein of alpha (ɑ) and beta (β) subunits. Under optimal oxygen conditions, HIF1β is present in the nucleus while HIF1ɑ remains in the cytosol. HIF1ɑ is hydroxylated by prolyl...
2.5K
01:17Intracellular Signaling Affects Focal Adhesions
2.6K
Integrins act both as extracellular input receivers and as intracellular processing activators. As their name suggests, integrins are entirely integrated into the membrane structure. Their hydrophobic membrane-spanning regions interact with the phospholipid bilayer's hydrophobic region. These membrane receptors provide extracellular attachment sites for effectors like hormones and growth factors. They activate intracellular response cascades when their effectors are bound and active.
Some...
Some...
2.6K
01:22Role of Ephrin-Eph Signalling in Intestinal Stem Cell Renewal
2.2K
Erythropoietin-producing hepatocellular carcinoma receptor (Eph) and its ligand, Eph receptor-interacting protein (Ephrin) were first discovered in the human carcinoma cell line, hence the name. Ephrin-Eph interaction guides cells to reach their appropriate location in adult tissues. They also play an essential role in the immune system by helping in immune cell migration, adhesion, and activation. Based on their structure and function, Eph is divided into two classes — EphA and EphB.
2.2K
01:09Cell Migration
16.9K
Cell migration, the process by which cells move from one location to another, is essential for the proper development and viability of organisms throughout their life. When cells are not able to migrate properly to their ordained locations, various disorders may occur. For example, disruption in cell migration causes chronic inflammatory diseases such as arthritis.
16.9K