Abstract
Proteins encoded by the fringe family of genes are required to modulate Notch signalling in a wide range of developmental contexts. Using a cell co-culture assay, we find that mammalian Lunatic fringe (Lfng) inhibits Jagged1-mediated signalling and potentiates Delta1-mediated signalling through Notch1. Lfng localizes to the Golgi, and Lfng-dependent modulation of Notch signalling requires both expression of Lfng in the Notch-responsive cell and the Notch extracellular domain. Lfng does not prevent binding of soluble Jagged1 or Delta1 to Notch1-expressing cells. Lfng potentiates both Jagged1- and Delta1-mediated signalling via Notch2, in contrast to its actions with Notch1. Our data suggest that Fringe-dependent differential modulation of the interaction of Delta/Serrate/Lag2 (DSL) ligands with their Notch receptors is likely to have a significant role in the combinatorial repertoire of Notch signalling in mammals.
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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Alkaline Phosphatase / genetics
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Alkaline Phosphatase / metabolism
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Animals
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Calcium-Binding Proteins
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Cell Line
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Coculture Techniques
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Fibroblasts
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Glucosyltransferases
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Glycosyltransferases*
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Golgi Apparatus / chemistry
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Golgi Apparatus / metabolism
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Intercellular Signaling Peptides and Proteins
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Intracellular Signaling Peptides and Proteins
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Jagged-1 Protein
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Ligands
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Membrane Proteins / chemistry
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Membrane Proteins / metabolism*
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Mice
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Muscles / cytology
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Muscles / metabolism
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Protein Binding
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Protein Structure, Tertiary
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Proteins / antagonists & inhibitors
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Proteins / genetics
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Proteins / metabolism*
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Receptor, Notch1
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Receptor, Notch2
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Receptors, Cell Surface / metabolism*
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Recombinant Fusion Proteins / metabolism
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Serrate-Jagged Proteins
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Signal Transduction*
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Transcription Factors*
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Transfection
Substances
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Calcium-Binding Proteins
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Intercellular Signaling Peptides and Proteins
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Intracellular Signaling Peptides and Proteins
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Jag1 protein, mouse
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Jagged-1 Protein
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Ligands
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Membrane Proteins
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Notch1 protein, mouse
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Notch2 protein, mouse
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Proteins
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Receptor, Notch1
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Receptor, Notch2
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Receptors, Cell Surface
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Recombinant Fusion Proteins
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Serrate-Jagged Proteins
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Transcription Factors
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delta protein
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Glycosyltransferases
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Glucosyltransferases
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Lfng protein, mouse
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Mfng protein, mouse
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Alkaline Phosphatase