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.
Publication types
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Research Support, Non-U.S. Gov't
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Research Support, U.S. Gov't, Non-P.H.S.
MeSH terms
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Adaptor Proteins, Vesicular Transport / metabolism
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Amino Acid Sequence
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Animals
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Animals, Genetically Modified / genetics
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Animals, Genetically Modified / metabolism
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Calcium-Binding Proteins / genetics
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Calcium-Binding Proteins / metabolism*
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Cell Membrane / genetics
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Cell Membrane / metabolism
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Conserved Sequence
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Drosophila Proteins / genetics
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Drosophila Proteins / metabolism*
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Drosophila melanogaster / genetics
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Drosophila melanogaster / metabolism*
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Endocytosis
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Female
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Gene Deletion
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Intercellular Signaling Peptides and Proteins / genetics
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Intercellular Signaling Peptides and Proteins / metabolism*
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Jagged-1 Protein
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Ligands
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Male
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Membrane Proteins / genetics
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Membrane Proteins / metabolism*
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Protein Binding
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Receptors, Notch / genetics
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Receptors, Notch / metabolism*
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Serrate-Jagged Proteins
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Signal Transduction
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Transcription Factors / genetics
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Transcription Factors / metabolism
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Transcriptional Activation
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Transfection
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Transgenes
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Wings, Animal / cytology
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Wings, Animal / metabolism
Substances
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Adaptor Proteins, Vesicular Transport
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Calcium-Binding Proteins
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Drosophila Proteins
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GAL4 protein, Drosophila
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Intercellular Signaling Peptides and Proteins
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Jagged-1 Protein
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Ligands
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Membrane Proteins
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N protein, Drosophila
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Receptors, Notch
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Ser protein, Drosophila
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Serrate-Jagged Proteins
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Transcription Factors
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epsin