Reversible and bidirectional signaling of notch ligands.

IF 6.2 2区 生物学 Q1 BIOCHEMISTRY & MOLECULAR BIOLOGY
Elenaé Vázquez-Ulloa, Kai-Lan Lin, Marcela Lizano, Cecilia Sahlgren
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引用次数: 1

Abstract

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.

缺口配体的可逆和双向信号传导。
Notch信号通路是一个直接的细胞-细胞通讯系统,参与多种生物过程,在多种病理中观察到它的破坏。该途径由表达配体的细胞(发送者)和表达受体的细胞(接收者)组成。规范配体是Delta/Serrate/Lag-1 (DSL)蛋白家族的成员。它们与邻近细胞中的Notch受体结合,诱导受体发生构象变化,从而发生受调控的膜内蛋白水解(RIP),释放Notch胞内结构域(NICD)。NICD易位到细胞核并促进基因转录。研究表明,这些配体也可以经历RIP和核易位,这表明配体在发送细胞中起作用,并且可能是Notch通路的双向性。虽然配体加工的完整机制尚不完全清楚,但它对Notch受体的依赖性也不排除。此外,配体具有Notch激活之外的自主功能。在这里,我们回顾了DSL蛋白的反向和双向信号的概念,并讨论了使它们不仅仅是Notch途径的配体的特征。
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来源期刊
CiteScore
14.90
自引率
0.00%
发文量
6
期刊介绍: As the discipline of biochemistry and molecular biology have greatly advanced in the last quarter century, significant contributions have been made towards the advancement of general medicine, genetics, immunology, developmental biology, and biophysics. Investigators in a wide range of disciplines increasingly require an appreciation of the significance of current biochemical and molecular biology advances while, members of the biochemical and molecular biology community itself seek concise information on advances in areas remote from their own specialties. Critical Reviews in Biochemistry and Molecular Biology believes that well-written review articles prove an effective device for the integration and meaningful comprehension of vast, often contradictory, literature. Review articles also provide an opportunity for creative scholarship by synthesizing known facts, fruitful hypotheses, and new concepts. Accordingly, Critical Reviews in Biochemistry and Molecular Biology publishes high-quality reviews that organize, evaluate, and present the current status of high-impact, current issues in the area of biochemistry and molecular biology. Topics are selected on the advice of an advisory board of outstanding scientists, who also suggest authors of special competence. The topics chosen are sufficiently broad to interest a wide audience of readers, yet focused enough to be within the competence of a single author. Authors are chosen based on their activity in the field and their proven ability to produce a well-written publication.
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