拉特罗菲林-2在内皮结处调解液体剪切应力机制传导
bioRxiv : the preprint server for biology
|June 25, 2024
概括
液体剪切应力通过拉特罗菲林-2 (Lphn-2/ADGRL2) 和G蛋白信号激活内皮细胞,影响血管发育和心血管疾病.
科学领域:
- 血管生物学 血管生物学
- 细胞信号传递 细胞信号传递
- 机械转导是指机械转导的过程.
背景情况:
- 内皮细胞对血流剪切应激的反应对血管健康至关重要.
- 在细胞结处的一个已知的复合体 (PECAM-1,VE-cadherin,VEGFRs,PlexinD1) 调解这些反应.
- 有证据表明,一个未知的机械传感器在PECAM-1上游起作用.
研究的目的:
- 为了确定上游机械传感器和信号通路,参与内皮细胞对剪切应力的反应.
- 研究G蛋白结合受体 (GPCRs) 和Gα蛋白在这个过程中的作用.
主要方法:
- 对Gα子单元的siRNA查,以确定关键参与者.
- 开发一种新型激活试验,以测量G蛋白通过流动的激活.
- 映射Gα激活残留物和亲和性净化以识别上游GPCR.
- 利用了小鼠和斑马鱼模型,以及内皮特异性淘汰,以及人类遗传数据.
主要成果:
- Gαi2和Gαq/11对于激活结合复合体来响应流动是必不可少的.
- 拉特罗菲林-2 (Lphn-2/ADGRL2) 被确定为上游GPCR激活这些G蛋白.
- Lphn-2对于PECAM-1下游信号,流量依赖性血管生成和动脉重塑在体内至关重要.
- 人类遗传数据将Lphn-2基因 (Adgrl2) 与心血管疾病联系起来.
结论:
- 定义了一个新的信号通路,将拉特罗菲林-2介导的G蛋白激活与内皮机械传导联系起来.
- 这一途径对血管生理学,发育至关重要,并与心血管疾病有关.
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