Abstract

To build a complex body composed of various cell types and tissues and to maintain tissue homeostasis in the postembryonic period, animals use a small number of highly conserved intercellular communication pathways. Among these is the Notch signaling pathway, which is mediated via the interaction of transmembrane Notch receptors and ligands usually expressed by neighboring cells. Maintaining optimal Notch pathway activity is essential for normal development, as evidenced by various human diseases caused by decreased and increased Notch signaling. It is therefore not surprising that multiple mechanisms are used to control the activation of this pathway in time and space. Over the last 20 years, protein glycosylation has been recognized as a major regulatory mechanism for Notch signaling. In this review, we will provide a summary of the various types of glycan that have been shown to modulate Notch signaling. Building on recent advances in the biochemistry, structural biology, cell biology and genetics of Notch receptors and the glycosyltransferases that modify them, we will provide a detailed discussion on how various steps during Notch activation are regulated by glycans. Our hope is that the current review article will stimulate additional research in the field of Notch glycobiology and will potentially be of benefit to investigators examining the contribution of glycosylation to other developmental processes.

中文翻译：

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通过糖基化对 Notch 信号进行多方面调控。

摘要

为了构建由各种细胞类型和组织组成的复杂体并在胚胎后期维持组织稳态，动物使用少量高度保守的细胞间通讯途径。其中包括 Notch 信号通路，它通过跨膜 Notch 受体和通常由相邻细胞表达的配体的相互作用介导。保持最佳的 Notch 通路活性对于正常发育至关重要，由 Notch 信号传导减少和增加引起的各种人类疾病证明了这一点。因此，使用多种机制在时间和空间上控制该通路的激活也就不足为奇了。在过去的 20 年中，蛋白质糖基化已被公认为 Notch 信号传导的主要调节机制。在本次审查中，我们将总结已显示可调节 Notch 信号传导的各种类型的聚糖。基于 Notch 受体和修饰它们的糖基转移酶的生物化学、结构生物学、细胞生物学和遗传学的最新进展，我们将详细讨论 Notch 激活过程中的各个步骤如何受到聚糖的调节。我们希望当前的评论文章将刺激 Notch 糖生物学领域的更多研究，并可能对研究糖基化对其他发育过程的贡献的研究人员有益。我们将详细讨论 Notch 激活过程中的各个步骤如何受聚糖的调节。我们希望当前的评论文章将刺激 Notch 糖生物学领域的更多研究，并可能对研究糖基化对其他发育过程的贡献的研究人员有益。我们将详细讨论 Notch 激活过程中的各个步骤如何受聚糖的调节。我们希望当前的评论文章将刺激 Notch 糖生物学领域的更多研究，并可能对研究糖基化对其他发育过程的贡献的研究人员有益。