近日，国际著名杂志PLoS One上刊登了来自中科院生物物理研究所和美国辛辛那提儿童研究基金会的研究人员的最新研究成果“Uif, a Large Transmembrane Protein with EGF-Like Repeats, Can Antagonize Notch Signaling in Drosophila，”，研究者在果蝇中证实一种具有EGF样重复序列（EGF like repeats）的大型跨膜蛋白Uif对抗了经典的Notch信号。
来自中科院生物物理研究所的焦仁杰研究院和美国辛辛那提儿童医院的马骏教授为这篇文章的共同通讯作者。焦仁杰自上世纪90年代中后期开始致力于果蝇发育的分子遗传调控研究，至今已在Dev. Cell, Development, Dev. Biol等专业期刊发表研究论文三十多篇。
Notch信号是在从果蝇到人类的多细胞生物体进化中一条高度保守的信号转导通路。它通过高度特异性的方式从空间上和时间上刺激靶基因表达调控着细胞增殖、分化和凋亡的功能涉及几乎所有组织和器官。Notch信号输出的多样性、特异性和敏感性在不同的水平，尤其在配体受体互作水平上受到调控。
在这篇文章中，研究人员证实果蝇的uninflatable (uif)基因编码了一种胞外域包含18个EGF样重复序列（EGF like repeats）的大型跨膜蛋白，并证实这一跨膜蛋白可以对抗经典的Notch信号通路。研究人员发现过表达Uif或异位表达Uif新变体形式Uif*，可导致果蝇翅和感觉器前体Notch信号缺陷。进一步的实验表明异位表达Uif*顺式抑制了Notch信号，这一步依赖于Notch的胞外域。研究结果表明Uif改变了Notch激活过程中Notch胞外域与配体的结合。
新研究证实了Uif可以调控Notch活性，表明了这一信号通路精微调控对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.
