内皮 discoidin 域受体 1 感知流动以调节 YAP 激活
Jiayu Liu1,2, Chuanrong Zhao1,2,3, Xue Xiao4
1Department of Physiology and Pathophysiology, School of Basic Medical Sciences, State Laboratory of Vascular Homeostasis and Remodeling, Peking University, Beijing, 100191, China.
Nature communications
|October 13, 2023
概括
迪斯科伊丁域受体1 (DDR1) 作为内皮细胞中的直接机械传感器,将剪切力转化为细胞反应. 它的流动诱导激活通过影响YAP信号来促进动脉样硬化.
科学领域:
- 心血管生物学 心血管生物学
- 细胞机械传导 细胞机械传导
- 分子信号传输的方法
背景情况:
- 内皮机械传导对于血管平衡至关重要,但特定的流量感应分子在很大程度上是未知的.
- 对机械力量的内皮细胞反应失调有助于诸如动脉样硬化等血管疾病.
研究的目的:
- 确定由内皮细胞感知和响应剪切应激的分子机制.
- 调查迪斯科伊丁域受体1 (DDR1) 在内皮细胞机械传导中的作用及其对动脉样硬化的贡献.
主要方法:
- 使用内皮细胞模型研究DDR1作为机械传感器的功能.
- 分析了DDR1.1的剪切诱导的形状变化,寡合化和相分离.
- 检查了下游的信号通路,包括YAP核转移,在DDR1激活后.
主要成果:
- 证明DDR1在内皮细胞中直接感知剪切力.
- 确定了DDR1的DS类域的流动诱导的展开和氨酸287.7的暴露.
- 展示了DDR1的寡合化,相位分离和与YWHAE的共同凝结,导致YAP的核转移.
- 确立了流动诱导的DDR1激活是异构的.
结论:
- DDR1作为内皮细胞中剪切应力的关键机械传感器.
- 通过流动激活DDR1,启动了一个信号级联,涉及生物分子凝聚物和YAP转位.
- 内皮DDR1激活代表了一种促进动脉样硬化的新机制.
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