Abstract
Activation of the Notch (N) receptor involves an intracellular proteolytic step triggered by shedding of the extracellular N domain (N-EC) upon ligand interaction. The ligand Dl has been proposed to effect this N-EC shedding by transendocytosing the latter into the signal-emitting cell. We find that Dl endocytosis and N signaling are greatly stimulated by expression of neuralized (neur). neur inactivation suppresses Dl endocytosis, while its overexpression enhances Dl endocytosis and Notch-dependent signaling. We show that neur encodes an intracellular peripheral membrane protein. Its C-terminal RING domain is necessary for Dl accumulation in endosomes, but may be dispensable for Dl signaling. The potent modulatory effect of Neur on Dl activity makes Neur a candidate for establishing signaling asymmetries within cellular equivalence groups.
Publication types
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Research Support, Non-U.S. Gov't
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Research Support, U.S. Gov't, P.H.S.
MeSH terms
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Animals
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Drosophila Proteins / genetics
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Drosophila Proteins / metabolism
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Drosophila melanogaster / embryology
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Drosophila melanogaster / physiology*
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Embryonic Structures / cytology
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Embryonic Structures / physiology
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Endocytosis / physiology*
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Genes, Reporter
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Intracellular Signaling Peptides and Proteins
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Ligases*
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Membrane Proteins / genetics
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Membrane Proteins / metabolism*
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Microscopy, Fluorescence
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Nerve Tissue Proteins / genetics
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Nerve Tissue Proteins / metabolism*
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Photoreceptor Cells, Invertebrate / cytology
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Photoreceptor Cells, Invertebrate / physiology
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Protein Structure, Tertiary
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Recombinant Fusion Proteins / metabolism
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Signal Transduction / physiology*
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Ubiquitin-Protein Ligases*
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Wings, Animal / cytology
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Wings, Animal / physiology
Substances
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Drosophila Proteins
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Intracellular Signaling Peptides and Proteins
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Membrane Proteins
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Nerve Tissue Proteins
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Recombinant Fusion Proteins
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delta protein
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Ubiquitin-Protein Ligases
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neur protein, Drosophila
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Ligases