title: Uif, a large transmembrane protein with EGF-like repeats, can antagonize Notch signaling in Drosophila.
abstract: 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.
  
  
  RESULTS
  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
  Our study shows that Uif can modulate Notch activity, illustrating the importance of a delicate regulation of this signaling pathway for normal patterning.
authors.affiliation: State Key Laboratory of Brain and Cognitive Science, Institute of Biophysics, Chinese Academy of Sciences, Beijing, China.
authors.forename: Gengqiang
authors.initials: G
authors.lastname: Xie
authors.forename: Hongtao
authors.initials: H
authors.lastname: Zhang
authors.forename: Guiping
authors.initials: G
authors.lastname: Du
authors.forename: Qinglei
authors.initials: Q
authors.lastname: Huang
authors.forename: Xuehong
authors.initials: X
authors.lastname: Liang
authors.forename: Jun
authors.initials: J
authors.lastname: Ma
authors.forename: Renjie
authors.initials: R
authors.lastname: Jiao
mesh_terms: D000818:Animals; D029721:Drosophila Proteins / Q000737:chemistry* / Q000235:genetics / Q000378:metabolism*; D004331:Drosophila melanogaster / Q000166:cytology* / Q000235:genetics / Q000378:metabolism; D004815:Epidermal Growth Factor / Q000737:chemistry*; D005109:Extracellular Matrix / Q000378:metabolism; D005786:Gene Expression Regulation; D008565:Membrane Proteins / Q000737:chemistry* / Q000235:genetics / Q000378:metabolism*; D017434:Protein Structure, Tertiary; D051880:Receptors, Notch / Q000737:chemistry / Q000378:metabolism*; D020449:Repetitive Sequences, Amino Acid; D015398:Signal Transduction
chemical_list: D029721:Drosophila Proteins; D008565:Membrane Proteins; C497759:N protein, Drosophila; D051880:Receptors, Notch; C545359:Uif protein, Drosophila; D004815:Epidermal Growth Factor