Uif, a large transmembrane protein with EGF-like repeats, can antagonize Notch signaling in Drosophila.
Uif, a large transmembrane protein with EGF-like repeats, can antagonize Notch signaling in Drosophila.
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DOI：
10.1371/journal.pone.0036362
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发表时间：
2012
期刊：
影响因子：
3.7
通讯作者：
Jiao R
中科院分区：
文献类型：
--
作者：
Xie G;Zhang H;Du G;Huang Q;Liang X;Ma J;Jiao R
Notch信号传导是从苍蝇到人类的多细胞生物中高度保守的途径。它通过刺激其靶基因在空间和时间上以高度特异性的方式表达来控制各种发育过程。Notch信号输出的多样性、特异性和敏感性在不同的水平上受到调节，特别是在配体-受体相互作用的水平上。在这里，我们报告说，果蝇基因uninflammable（uif），它编码一个大的跨膜蛋白与18 EGF样重复在其细胞外结构域，可以拮抗经典的Notch信号通路。Uif的过度表达或Uif的新变体Uif * 的异位表达导致翅膀和感觉器官前体两者中的Notch信号传导缺陷。进一步的实验表明，Uif* 的异位表达抑制Notch顺式信号传导，并在依赖于Notch的细胞外结构域的步骤中起作用。我们的研究结果表明，UIF可以改变Notch激活过程中Notch细胞外结构域对其配体的可及性。我们的研究表明，Uif可以调节Notch活性，说明了这种信号通路的正常模式的微妙调节的重要性。
Notch signaling is a highly conserved pathway in multi-cellular organisms ranging from flies to humans. It controls a variety of developmental processes by stimulating the expression of its target genes in a highly specific manner both spatially and temporally. The diversity, specificity and sensitivity of the Notch signaling output are regulated at distinct levels, particularly at the level of ligand-receptor interactions. Here, we report that the Drosophila gene uninflatable (uif), which encodes a large transmembrane protein with eighteen EGF-like repeats in its extracellular domain, can antagonize the canonical Notch signaling pathway. Overexpression of Uif or ectopic expression of a neomorphic form of Uif, Uif*, causes Notch signaling defects in both the wing and the sensory organ precursors. Further experiments suggest that ectopic expression of Uif* inhibits Notch signaling in cis and acts at a step that is dependent on the extracellular domain of Notch. Our results suggest that Uif can alter the accessibility of the Notch extracellular domain to its ligands during Notch activation. Our study shows that Uif can modulate Notch activity, illustrating the importance of a delicate regulation of this signaling pathway for normal patterning.
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