An extracellular region of Serrate is essential for ligandinduced cis-inhibition of Notch signaling

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Abstract

Cell-to-cell communication via the Notch pathway is mediated between the membrane-bound Notch receptor and either of its canonical membrane-bound ligands Delta or Serrate. Notch ligands mediate receptor transactivation between cells and also mediate receptor cis-inhibition when Notch and ligand are co-expressed on the same cell. We demonstrate in Drosophila that removal of any of the EGF-like repeats (ELRs) 4, 5 or 6 results in a Serrate molecule capable of transactivating Notch but exhibiting little or no Notch cis-inhibition capacity. These forms of Serrate require Epsin (Liquid facets) to transduce a signal, suggesting that ELR 4-6-deficient ligands still require endocytosis for Notch activation. We also demonstrate that ELRs 4-6 are responsible for the dominant-negative effects of Serrate ligand forms that lack the intracellular domain and are therefore incapable of endocytosis in the ligand-expressing cell. We find that ELRs 4-6 of Serrate are conserved across species but do not appear to be conserved in Delta homologs. © 2013. Published by The Company of Biologists Ltd.

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Fleming, R. J., Hori, K., Sen, A., Filloramo, G. V., Langer, J. M., Obar, R. A., … Maharaj-Best, A. C. (2013). An extracellular region of Serrate is essential for ligandinduced cis-inhibition of Notch signaling. Development (Cambridge), 140(9), 2039–2049. https://doi.org/10.1242/dev.087916

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