一个非正规的Notch复合体调节粘附结和血管屏障功能
William J Polacheck1,2, Matthew L Kutys1,2, Jinling Yang1,2
1The Wyss Institute for Biologically Inspired Engineering, Harvard University, Boston, Massachusetts, USA.
Nature
|November 22, 2017
概括
剪切压力激活NOTCH1,一个对血管屏障完整性的受体. 这种非正规的途径,独立于转录,使用NOTCH1的跨膜域组装附着结并维持血管功能.
科学领域:
- 血管生物学
- 细胞信号传输
- 生物物理
背景情况:
- 内皮形成一个重要的血管屏障, 调节运输和炎症.
- 血动力学剪切应力对内皮屏障功能至关重要,但其潜在机制尚不清楚.
研究的目的:
- 阐明剪切应力维持内皮屏障功能的机制.
- 研究NOTCH1在调节血管屏障完整性的作用.
主要方法:
- 使用透式微容器的机器模型.
- 使用小鼠模型验证结果.
- 研究了NOTCH1激活及其对附着基结的下游影响.
主要成果:
- 剪切应激触发了NOTCH1的DLL4依赖激活,暴露了其跨膜域.
- NOTCH1 跨膜域足以恢复内皮屏障功能.
- 这一域促进了激活RAC1的受体复合体 (VE-cadherin,LAR,TRIO),驱动了粘附结组件.
结论:
- 一个非正规的,转录独立的NOTCH1信号通路调节血管屏障功能.
- 这一途径将转录程序与细胞骨架重塑通过附着结合组合联系起来.
- NOTCH1在血管生物学中起着双重作用,包括正规的转录和非正规的信号传递.
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