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首页> 外文期刊>Molecular membrane biology >Endocytic regulation of Notch activation and down-regulation (review).
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Endocytic regulation of Notch activation and down-regulation (review).

机译：Notch激活的内吞调节和下调（综述）。

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摘要

Notch receptor signalling plays a central role in development and its misfunction has been linked to a number of diseases. In the cannonical Notch signalling pathway, ligand binding to Notch activates a series of proteolytic cleavages that release the Notch intracellular domain for trafficking to the nucleus, where it activates the transcription factor, Suppressor of Hairless (Su(H)). A number of recent papers have demonstrated the importance of endocytic trafficking of Notch and its ligands for both the activation and the down-regulation of the Notch receptor. These reports highlight uncertainty regarding the whereabouts in the cell where Notch activation occurs, and the form of the ligand that can induce signalling. In this review we speculate that, decision points between alternative trafficking pathways represent important regulatory nodes that may allow Notch signalling levels to be modulated by other developmental signals, providing context-dependency to Notch activation. We also review data thatsuggest that key proteolytic events, associated with Notch activation, may occur within the endocytic pathway or require prior endocytosis and recycling of Notch and its ligands to the cell surface. Sorting within the endocytic pathway, regulated by several different ubiquitin ligase proteins, may be involved in ensuring whether ligand and receptor are competent to signal. Furthermore, the utilisation of an alternative mechanism of Notch signalling, independent of Su(H), may depend on driving endocytic Notch into a specific compartment, in response to the activity of the ring finger domain protein, Deltex.
机译：Notch受体信号传导在发育中起着核心作用，其功能异常与许多疾病有关。在规范的Notch信号通路中，与Notch结合的配体激活了一系列蛋白水解裂解，释放出Notch细胞内结构域以转运至细胞核，并在其中激活了转录因子无毛抑制因子（Su（H））。最近的许多论文已经证明了Notch及其配体的内吞运输对于Notch受体的激活和下调都具有重要意义。这些报告突出了关于Notch激活发生在细胞中的下落以及可以诱导信号传导的配体形式的不确定性。在这篇综述中，我们推测，替代性贩运途径之间的决定点代表重要的调控节点，这些节点可能允许Notch信号水平被其他发育信号调节，从而为Notch激活提供了背景依赖性。我们还审查了数据，这些数据提示与Notch激活相关的关键蛋白水解事件可能发生在内吞途径内，或者需要事先进行内吞并将Notch及其配体回收到细胞表面。内吞途径内的分选受几种不同的泛素连接酶蛋白调节，可能参与确保配体和受体是否具有信号传导能力。此外，Notch信号传导的另一种机制的独立于Su（H）的利用，可能取决于响应无名指结构域蛋白Deltex的活性，将内吞性Notch驱动进入特定的区室。

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