Sprinzak David, Blacklow Stephen C
George S. Wise Faculty of Life Sciences, School of Neurobiology, Biochemistry, and Biophysics, Tel Aviv University, Tel Aviv 69978, Israel; email:
Department of Biological Chemistry and Molecular Pharmacology, Blavatnik Institute, Harvard Medical School, Boston, Massachusetts 02115, USA; email:
Annu Rev Biophys. 2021 May 6;50:157-189. doi: 10.1146/annurev-biophys-101920-082204. Epub 2021 Feb 3.
Notch signaling is a conserved system of communication between adjacent cells, influencing numerous cell fate decisions in the development of multicellular organisms. Aberrant signaling is also implicated in many human pathologies. At its core, Notch has a mechanotransduction module that decodes receptor-ligand engagement at the cell surface under force to permit proteolytic cleavage of the receptor, leading to the release of the Notch intracellular domain (NICD). NICD enters the nucleus and acts as a transcriptional effector to regulate expression of Notch-responsive genes. In this article, we review and integrate current understanding of the detailed molecular basis for Notch signal transduction, highlighting quantitative, structural, and dynamic features of this developmentally central signaling mechanism. We discuss the implications of this mechanistic understanding for the functionality of the signaling pathway in different molecular and cellular contexts.
Notch信号传导是相邻细胞间保守的通讯系统，影响多细胞生物体发育过程中众多细胞命运的决定。异常信号传导也与许多人类疾病有关。其核心是，Notch有一个机械转导模块，该模块在受力情况下解码细胞表面的受体-配体结合，以允许受体进行蛋白水解切割，从而导致Notch细胞内结构域（NICD）的释放。NICD进入细胞核并作为转录效应因子调节Notch反应性基因的表达。在本文中，我们回顾并整合了目前对Notch信号转导详细分子基础的理解，突出了这一发育核心信号机制的定量、结构和动态特征。我们讨论了这种机制理解对信号通路在不同分子和细胞背景下功能的影响。
