Vázquez-Ulloa Elenaé, Lin Kai-Lan, Lizano Marcela, Sahlgren Cecilia
Faculty of Science and Engineering/Cell Biology, Åbo Akademi University, Turku, Finland.
Turku Bioscience, University of Turku and Åbo Akademi University, Turku, Finland.
Crit Rev Biochem Mol Biol. 2022 Aug;57(4):377-398. doi: 10.1080/10409238.2022.2113029. Epub 2022 Sep 1.
The Notch signaling pathway is a direct cell-cell communication system involved in a wide variety of biological processes, and its disruption is observed in several pathologies. The pathway is comprised of a ligand-expressing (sender) cell and a receptor-expressing (receiver) cell. The canonical ligands are members of the Delta/Serrate/Lag-1 (DSL) family of proteins. Their binding to a Notch receptor in a neighboring cell induces a conformational change in the receptor, which will undergo regulated intramembrane proteolysis (RIP), liberating the Notch intracellular domain (NICD). The NICD is translocated to the nucleus and promotes gene transcription. It has been demonstrated that the ligands can also undergo RIP and nuclear translocation, suggesting a function for the ligands in the sender cell and possible bidirectionality of the Notch pathway. Although the complete mechanism of ligand processing is not entirely understood, and its dependence on Notch receptors has not been ruled out. Also, ligands have autonomous functions beyond Notch activation. Here we review the concepts of reverse and bidirectional signalization of DSL proteins and discuss the characteristics that make them more than just ligands of the Notch pathway.
Notch信号通路是一种直接的细胞间通讯系统，参与多种生物学过程，并且在多种病理状态下可观察到该通路的破坏。该通路由一个表达配体的（信号发送）细胞和一个表达受体的（信号接收）细胞组成。典型的配体是Delta/Serrate/Lag-1（DSL）蛋白家族的成员。它们与相邻细胞中的Notch受体结合会诱导受体发生构象变化，该受体会经历调节性膜内蛋白水解（RIP），释放出Notch胞内结构域（NICD）。NICD易位至细胞核并促进基因转录。已经证明配体也可以进行RIP和核易位，这表明配体在信号发送细胞中具有功能，并且Notch信号通路可能具有双向性。尽管配体加工的完整机制尚未完全阐明，并且其对Notch受体的依赖性也未被排除。此外，配体具有Notch激活以外的自主功能。在此，我们综述DSL蛋白的反向和双向信号传导概念，并讨论使其不仅仅是Notch信号通路配体的特征。
