Abstract
Ligands that are capable of activating Notch family receptors are broadly expressed in animal development, but their activity is tightly regulated to allow formation of tissue boundaries. Members of the fringe gene family have been implicated in limiting Notch activation during boundary formation, but the mechanism of Fringe function has not been determined. Here we present evidence that Fringe acts in the Golgi as a glycosyltransferase enzyme that modifies the epidermal growth factor (EGF) modules of Notch and alters the ability of Notch to bind its ligand Delta. Fringe catalyses the addition of N-acetylglucosamine to fucose, which is consistent with a role in the elongation of O-linked fucose O-glycosylation that is associated with EGF repeats. We suggest that cell-type-specific modification of glycosylation may provide a general mechanism to regulate ligand-receptor interactions in vivo.
Publication types
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Research Support, Non-U.S. Gov't
MeSH terms
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Alkaline Phosphatase / genetics
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Alkaline Phosphatase / metabolism
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Animals
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Binding Sites
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Cells, Cultured
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Cloning, Molecular
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Drosophila
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Drosophila Proteins
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Epidermal Growth Factor / metabolism
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Fucose / metabolism
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Glycosyltransferases / genetics
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Glycosyltransferases / metabolism*
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Golgi Apparatus / metabolism
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Insect Proteins / genetics
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Insect Proteins / metabolism
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Intracellular Signaling Peptides and Proteins
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Membrane Proteins / genetics
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Membrane Proteins / metabolism*
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N-Acetylglucosaminyltransferases*
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Protein Binding
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Protein Structure, Tertiary
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Receptors, Notch
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Recombinant Fusion Proteins / genetics
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Recombinant Fusion Proteins / metabolism
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Repetitive Sequences, Amino Acid
Substances
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Drosophila Proteins
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Insect Proteins
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Intracellular Signaling Peptides and Proteins
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Membrane Proteins
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N protein, Drosophila
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Receptors, Notch
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Recombinant Fusion Proteins
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delta protein
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Fucose
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Epidermal Growth Factor
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Glycosyltransferases
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N-Acetylglucosaminyltransferases
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fng protein, Drosophila
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Alkaline Phosphatase