Inhibition of Wnt signalling by Notch via two distinct mechanisms.
Inhibition of Wnt signalling by Notch via two distinct mechanisms.
复制标题
Notch通过两种不同的机制抑制Wnt信号传导。
DOI：
10.1038/s41598-021-88618-5
复制
发表时间：
2021-04-27
影响因子：
4.6
通讯作者：
Brennan K
中科院分区：
文献类型：
--
作者：
Acar A;Hidalgo-Sastre A;Leverentz MK;Mills CG;Woodcock S;Baron M;Collu GM;Brennan K
Notch和Wnt是帮助动物在发育过程中形成和维持成年组织稳态的两个重要信号通路。尽管它们通常在组织内同时活跃，但它们通常对细胞命运的决定有相反的影响。事实上，这两种途径之间的相互作用对于产生我们在后生动物中发现的细胞类型的巨大多样性非常重要。已经提出了几种不同的机制，允许Notch限制Wnt信号，驱动Notch- on /Wnt- off状态。在这里，我们探索了人类细胞中这些不同的机制，并证明了Notch本身可以限制β-catenin转录活性的两种不同机制。在膜上，独立于DSL配体，Notch1可以通过内吞机制拮抗β-catenin活性，该机制需要与Deltex相互作用并将β-catenin隔离到膜组分中。在细胞核内，Notch1的胞内结构域也可以通过形成需要与RBPjκ相互作用的复合物来限制β-catenin诱导的转录。我们相信这些机制通过强化对立Notch/Wnt反应之间的区别，有助于细胞命运决定的稳健性。
Notch and Wnt are two essential signalling pathways that help to shape animals during development and to sustain adult tissue homeostasis. Although they are often active at the same time within a tissue, they typically have opposing effects on cell fate decisions. In fact, crosstalk between the two pathways is important in generating the great diversity of cell types that we find in metazoans. Several different mechanisms have been proposed that allow Notch to limit Wnt signalling, driving a Notch-ON/Wnt-OFF state. Here we explore these different mechanisms in human cells and demonstrate two distinct mechanisms by which Notch itself, can limit the transcriptional activity of β-catenin. At the membrane, independently of DSL ligands, Notch1 can antagonise β-catenin activity through an endocytic mechanism that requires its interaction with Deltex and sequesters β-catenin into the membrane fraction. Within the nucleus, the intracellular domain of Notch1 can also limit β-catenin induced transcription through the formation of a complex that requires its interaction with RBPjκ. We believe these mechanisms contribute to the robustness of cell-fate decisions by sharpening the distinction between opposing Notch/Wnt responses.
登录
查看更多内容
突变动力蛋白的诱导特异性阻断内吞涂层囊泡的形成。
影响因子：
7.8
作者：
Damke, H;Baba, T;Warnock, D E;Schmid, S L
通讯作者：
Schmid, S L
影响因子：
3.3
作者：
Bishop, N;Woodmane, P
通讯作者：
Woodmane, P
影响因子：
64.5
作者：
Shimizu H;Woodcock SA;Wilkin MB;Trubenová B;Monk NA;Baron M
通讯作者：
Baron M
影响因子：
64.8
作者：
Reya, T;Clevers, H
通讯作者：
Clevers, H
影响因子：
4.8
作者：
Kuroda, K;Tani, S;Honjo, T
通讯作者：
Honjo, T