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Glycosyltransferase activity of Fringe modulates Notch–Delta interactions

Nature volume 406, pages 411–415 (2000)Cite this article

An Erratum to this article was published on 05 October 2000

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 boundaries1. Members of the fringe gene family have been implicated in limiting Notch activation during boundary formation2,3,4,5,6,7,8, 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.

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Figure 1: Fringe increases binding of Delta to Notch.
Figure 2: Golgi-tethered Fringe increases binding of Delta to Notch.
Figure 3: Fringe has glycosyltransferase activity.
Figure 4: Secreted Notch produced by Fringe–GT-expressing cells binds Delta-expressing cells.
Figure 5: Glycosylation of Notch by Fringe in vitro.

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Acknowledgements

We thank T. Nilsson for information about Golgi retention sequences; V. Malhotra for antibody to Drosophila Golgi; M. Fortini for Notch and Delta expression plasmids; A.-M. Voie for transgenic strains and F. Peverali for his contributions at an early stage of the work. K.B. thanks K. Prydz and D. Toomre for technical discussion; B. Keck and T. Schwientek for introduction to glycosyltransferase assays. H.C. is supported by the Danish Cancer Center and the Velux Foundation.

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  1. Katja Brückner

    Present address: Department of Genetics, Harvard Medical School, Howard Hughes Medical Institute, 200 Longwood Avenue, Boston, MA, 02115, USA

Authors and Affiliations

  1. European Molecular Biology Laboratory, Meyerhofstr 1, Heidelberg, 69117, Germany

    Katja Brückner, Lidia Perez & Stephen Cohen

  2. School of Dentistry, University of Copenhagen, Norre Alle 20, Copenhagen N, Dk2200, Denmark

    Henrik Clausen

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Correspondence to Stephen Cohen.

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Brückner, K., Perez, L., Clausen, H. et al. Glycosyltransferase activity of Fringe modulates Notch–Delta interactions . Nature 406, 411–415 (2000). https://doi.org/10.1038/35019075

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