期刊
DEVELOPMENT
卷 140, 期 9, 页码 2039-2049出版社
COMPANY OF BIOLOGISTS LTD
DOI: 10.1242/dev.087916
关键词
Notch; Cis-inhibition; Serrate ligand; Extracellular domain
资金
- National Science Foundation
- Faculty Research Council of Trinity College, Hartford, CT, USA
- National Institutes of Health
- Direct For Biological Sciences
- Division Of Integrative Organismal Systems [1121214] Funding Source: National Science Foundation
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.
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