Fringe Modulation of Jagged1-Induced Notch Signaling Requires the Action of β4galactosyltransferase-1

Fringe modulates Notch signaling resulting in the establishment of compartmental boundaries in developing organisms. Fringe is a β3N-acetylglucosaminyltransferase (β3GlcNAcT) that transfers GlcNAc to O-fucose in epidermal growth factor-like repeats of Notch. Here we use five different Chinese hamste...

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Published inProceedings of the National Academy of Sciences - PNAS Vol. 98; no. 24; pp. 13716 - 13721
Main Authors Chen, Jihua, Moloney, Daniel J., Stanley, Pamela
Format Journal Article
LanguageEnglish
Published National Academy of Sciences 20.11.2001
National Acad Sciences
The National Academy of Sciences
Subjects
Biological Sciences
CHO cells
Disaccharides
Drosophila
Fringe
L cells
Ligands
Modulated signal processing
Polysaccharides
Tetrasaccharides
Trisaccharides
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Summary:Fringe modulates Notch signaling resulting in the establishment of compartmental boundaries in developing organisms. Fringe is a β3N-acetylglucosaminyltransferase (β3GlcNAcT) that transfers GlcNAc to O-fucose in epidermal growth factor-like repeats of Notch. Here we use five different Chinese hamster ovary cell glycosylation mutants to identify a key aspect of the mechanism of fringe action. Although the β3GlcNAcT activity of manic or lunatic fringe is shown to be necessary for inhibition of Jagged1-induced Notch signaling in a coculture assay, it is not sufficient. Fringe fails to inhibit Notch signaling if the disaccharide generated by fringe action, GlcNAcβ3Fuc, is not elongated. The trisaccharide, Galβ4GlcNAcβ3Fuc, is the minimal O-fucose glycan to support fringe modulation of Notch signaling. Of six β4galactosyltransferases (β4GalT) in Chinese hamster ovary cells, only β4GalT-1 is required to add Gal to GlcNAcβ3Fuc, identifying β4GalT-1 as a new modulator of Notch signaling.
Bibliography:To whom reprint requests should be addressed. E-mail: stanley@aecom.yu.edu.
Edited by Sen-itiroh Hakomori, Pacific Northwest Research Institute, Seattle, WA, and approved September 12, 2001
ISSN:0027-8424
1091-6490
DOI:10.1073/pnas.241398098