Uif, a large transmembrane protein with EGF-like repeats, can antagonize Notch signaling in Drosophila.

PloS One
Gengqiang XieRenjie Jiao

Abstract

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 norm...Continue Reading

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Citations

Jun 26, 2013·Journal of Genetics and Genomics = Yi Chuan Xue Bao·Chuanxian WeiRenjie Jiao
Aug 27, 2014·Current Biology : CB·Sylvain LoubéryMarcos Gonzalez-Gaitan
Jul 19, 2015·Developmental and Comparative Immunology·Xiang-Jun RaoXiao-Qiang Yu
Jun 12, 2016·Development·Dominik StappertSiegfried Roth
Mar 26, 2021·Science Translational Medicine·In-Hyuk JungNathan O Stitziel

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