Fringe differentially modulates Jagged1 and Delta1 signalling through Notch1 and Notch2

• Published in: Nature cell biology Vol. 2; no. 8; pp. 515 - 520
• Main Authors: Vogt, Thomas F, Weinmaster, Gerry, Hicks, Carol, Johnston, Stuart H, diSibio, Guy, Collazo, Andres
• Format: Journal Article
• Language: English
• Published: England Nature Publishing Group 01.08.2000
• Subjects: Alkaline Phosphatase - genetics; Alkaline Phosphatase - metabolism; Animals; Calcium-Binding Proteins; Cell Line; Cell receptors; Cellular signal transduction; Coculture Techniques; Delta1 protein; Drosophila; Fibroblasts; Fringe genes; Genes; Genetic aspects; Glycosyltransferases; Golgi Apparatus - chemistry; Golgi Apparatus - metabolism; Insects; Intercellular Signaling Peptides and Proteins; Intracellular Signaling Peptides and Proteins; Jagged-1 Protein; Jagged1 protein; Ligands; Lunatic fringe protein; Mammalia; Mammals; Membrane Proteins - chemistry; Membrane Proteins - metabolism; Mice; Molecular biology; Muscles - cytology; Muscles - metabolism; Neurosciences; Notch receptors; Phosphatase; Physiological aspects; Plasmids; Protein Binding; Protein Structure, Tertiary; Proteins; Proteins - antagonists & inhibitors; Proteins - genetics; Proteins - metabolism; Receptor, Notch1; Receptor, Notch2; Receptors, Cell Surface - metabolism; Recombinant Fusion Proteins - metabolism; Serrate-Jagged Proteins; Signal Transduction; Transcription Factors; Transfection; Los Angeles California; United States > US; California
• ISSN: 1465-7392; 1476-4679; 1476-4679
• DOI: 10.1038/35019553

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.