时间动力学和静态测量在切口信号 - 从切口突触复合体形成到NICD核入口
bioRxiv : the preprint server for biology
|October 9, 2023
概括
这项研究可视化了实时的Notch信号传输动态. 在Notch细胞内域 (NICD) 进入细胞核之前,Notch和Delta形成了短暂的突触,揭示了精确的信号定时.
科学领域:
- 细胞和分子生物学 细胞和分子生物学
- 发展生物学 发展生物学
- 信号传输 信号传输
背景情况:
- 哺乳动物痕信号传递对于细胞命运的决定和发育至关重要.
- 这一途径涉及将连接体 (Delta/Jagged) 结合到Notch受体,导致NICD释放和核转位.
- 在生理条件下,这些事件的精确时间序列在很大程度上仍然没有特征.
研究的目的:
- 为了阐明信号发送期间的Notch和Delta相互作用的时空动态.
- 为了将细胞-细胞接触事件与Notch细胞内域 (NICD) 核积累相关联.
- 了解在本地细胞环境中Notch通路激活的实时动力学.
主要方法:
- 哺乳动物细胞中Notch和Delta蛋白的内源光标记.
- 活细胞成像可视化细胞与细胞接触时的蛋白质动态.
- 药理和遗传抑制以评估信号通路依赖性.
主要成果:
- 诺奇和德尔塔蛋白在细胞接触部位迅速形成1:1的静态测量突触,在15-20分钟内消失.
- 突触的形成先于Notch细胞外域的内部化和NICD核积累.
- 接触后大约45分钟,NICD水平达到峰值,并被化学和遗传阻塞剂抑制.
结论:
- 这项研究确立了诺奇-德尔塔突触形成与NICD产生之间的直接时间联系.
- 这些发现为Notch信号事件提供了前所未有的时空分辨率.
- 这种详细的理解对于破译Notch通路在发育和疾病中的作用至关重要.
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