在痕信号通路中的动态连接体歧视
Nagarajan Nandagopal1, Leah A Santat1, Lauren LeBon2
1Howard Hughes Medical Institute and Division of Biology and Biological Engineering, California Institute of Technology, Pasadena, CA 91125, USA.
Cell
|February 6, 2018
概括
细胞使用信号动态通过Notch1受体区分Dll1和Dll4联体. 这种动态信号控制着不同的目标基因表达和生物结果,揭示出一种新的通信机制.
科学领域:
- 细胞生物学
- 发育生物学
- 分子信号
背景情况:
- 这种信号通道对于细胞间的通信至关重要.
- 不同的Notch配体存在,但细胞如何区分它们仍然不清楚.
研究的目的:
- 研究细胞区分Dll1和Dll4接体的机制.
- 了解连体特异信号动态如何调节目标基因表达和细胞功能.
主要方法:
- 对Notch1受体激活的量化单细胞成像.
- 对Notch目标基因 (Hes1,Hey1,HeyL) 表达的分析.
- 在小神经细胞中,Dll1和Dll4的异位表达.
- 化学配体分析以研究配体与受体的相互作用.
主要成果:
- Dll1通过频率调节的脉冲激活了Notch1, 调节了Hes1.
- Dll4通过持续的振幅调节信号激活了Notch1,从而调节了Hey1和HeyL.
- 在体内实验表明Dll1和Dll4对肌体分化有相反的影响.
- 联体受体聚合与联体身份的动态编码有关.
结论:
- 细胞动力学,特别是信号脉冲频率和振幅,是区分Notch配体的关键.
- 这种由Notch1进行的配体歧视对各种发育过程有重大影响.
- 这些发现揭示了诺奇通道内的复杂通信系统.
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