近日,，國際著名雜志PLoS One上刊登了來自中科院生物物理研究所和美國辛辛那提兒童研究基金會的研究人員的最新研究成果“Uif, a Large Transmembrane Protein with EGF-Like Repeats, Can Antagonize Notch Signaling in Drosophila,，”，研究者在果蠅中證實一種具有EGF樣重復(fù)序列（EGF like repeats）的大型跨膜蛋白Uif對抗了經(jīng)典的Notch信號,。
來自中科院生物物理研究所的焦仁杰研究院和美國辛辛那提兒童醫(yī)院的馬駿教授為這篇文章的共同通訊作者,。焦仁杰自上世紀(jì)90年代中后期開始致力于果蠅發(fā)育的分子遺傳調(diào)控研究，至今已在Dev. Cell, Development, Dev. Biol等專業(yè)期刊發(fā)表研究論文三十多篇,。
Notch信號是在從果蠅到人類的多細(xì)胞生物體進化中一條高度保守的信號轉(zhuǎn)導(dǎo)通路,。它通過高度特異性的方式從空間上和時間上刺激靶基因表達調(diào)控著細(xì)胞增殖,、分化和凋亡的功能涉及幾乎所有組織和器官。Notch信號輸出的多樣性,、特異性和敏感性在不同的水平,，尤其在配體受體互作水平上受到調(diào)控。
在這篇文章中,，研究人員證實果蠅的uninflatable (uif)基因編碼了一種胞外域包含18個EGF樣重復(fù)序列（EGF like repeats）的大型跨膜蛋白,，并證實這一跨膜蛋白可以對抗經(jīng)典的Notch信號通路。研究人員發(fā)現(xiàn)過表達Uif或異位表達Uif新變體形式Uif*,，可導(dǎo)致果蠅翅和感覺器前體Notch信號缺陷,。進一步的實驗表明異位表達Uif*順式抑制了Notch信號，這一步依賴于Notch的胞外域,。研究結(jié)果表明Uif改變了Notch激活過程中Notch胞外域與配體的結(jié)合,。
新研究證實了Uif可以調(diào)控Notch活性，表明了這一信號通路精微調(diào)控對于正常模式的重要性,。（生物谷Bioon.com）
doi:10.1371/journal.pone.0036362
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Uif, a Large Transmembrane Protein with EGF-Like Repeats, Can Antagonize Notch Signaling in Drosophila
Gengqiang Xie1,2,3#, Hongtao Zhang1,2#, Guiping Du1,2, Qinglei Huang1, Xuehong Liang1, Jun Ma3,4*, Renjie Jiao1*
Background 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. Methodology/Principal Findings 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. Conclusions/Significance Our study shows that Uif can modulate Notch activity, illustrating the importance of a delicate regulation of this signaling pathway for normal patterning.
