一个时空的Notch相互作用地图,从等离子体膜到核.
Alexandre P Martin1, Gary A Bradshaw2, Robyn J Eisert1
1Department of Biological Chemistry and Molecular Pharmacology, Blavatnik Institute, Harvard Medical School, Boston, MA 02115, USA.
Science signaling
|August 1, 2023
概括
切口信号传输涉及切口受体的分裂,以释放核效应器. 这项研究绘制了Notch受体蛋白解和核转移的精确时间和位置,揭示了关键信号事件.
科学领域:
- 细胞生物学 细胞生物学
- 分子生物学分子生物学
- 生物化学 生物化学
背景情况:
- 痕信号对于细胞命运的决定至关重要.
- 干结合触发了诺奇受体蛋白解,释放了诺奇细胞内域 (NICD).
- NICD转移到细胞核,以调节基因转录.
研究的目的:
- 为了精确地绘制Notch受体处理的时空动态.
- 为了确定 Notch 分裂事件的细胞内位置和时间.
- 了解诺奇核复合体形成和基因诱导的动力学.
主要方法:
- 使用了近距离标记技术.
- 采用了定量,多重重的质谱学.
- 监测内源NOTCH2相互作用伙伴在对连接体刺激和玛分泌酶抑制的反应中.
主要成果:
- 玛分泌酶介导的NOTCH2的裂变发生在细胞内.
- 核复合体的形成和染色体修饰剂的招募发生在抑制剂洗后的45分钟内.
- 详细的时空地图的Notch从等离子膜到核的贩运产生.
结论:
- 阐明了Notch受体激活和核转位的逐步途径.
- 识别了可接受治疗调制的特定信号事件.
- 提供了关于细胞过程中Notch信号的动态调节的见解.
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