Glycosyltransferase activity of Fringe modulates Notch–Delta interactions

@article{Brckner2000GlycosyltransferaseAO,
  title={Glycosyltransferase activity of Fringe modulates Notch–Delta interactions},
  author={Katja Br{\"u}ckner and L{\'i}dia P{\'e}rez and H. Clausen and S. Cohen},
  journal={Nature},
  year={2000},
  volume={406},
  pages={411-415}
}
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… Expand
In Vitro Reconstitution of the Modulation of Drosophila Notch-Ligand Binding by Fringe*
TLDR
In vitro glycosylation and ligand binding studies establish that the addition of N-acetylglucosamine onto O-fucose in vitro is sufficient both to enhance Notch binding to the Delta ligand and to inhibit Notchbinding to the Serrate ligand. Expand
Modulation of Notch-Ligand Binding by Protein O-Fucosyltransferase 1 and Fringe*
TLDR
Assayed the ability of tagged, soluble forms of the Notch extracellular domain to bind to its ligands, Delta and Serrate, and found that Notch-ligand interactions are dependent upon both the presence and the type of O-fucose glycans. Expand
Fringe gives a saccharine to notch
TLDR
It is demonstrated that elongation of O-linked fucose on glycosylated proteins can act as an as-yet-unknown post-translational regulatory mechanism for modulating receptor–ligand interactions in signal transduction. Expand
Regions of Drosophila Notch That Contribute to Ligand Binding and the Modulatory Influence of Fringe*
TLDR
The observations imply that glycosylation influences Notch-ligand interactions through a distributive mechanism that involves local interactions with multiple EGF domains and led to a structural model for how Notch interacts with its ligands. Expand
Glycosylation of Specific Notch EGF Repeats by O-Fut1 and Fringe Regulates Notch Signaling in Drosophila
TLDR
The work shows the combinatorial and context-dependent roles of GlcNAc-fucose-O glycans on these sites in Drosophila Notch-ligand interactions, which are essential for Delta-mediated lateral inhibition in embryos and wing vein development. Expand
Chaperone Activity of Protein O-Fucosyltransferase 1 Promotes Notch Receptor Folding
TLDR
In Drosophila, Protein O-fucosyltransferase 1 (OFUT1), an enzyme that glycosylates epidermal growth factor–like domains of Notch, also has a distinct Notch chaperone activity that can bind its substrate in the endoplasmic reticulum to facilitate normal folding. Expand
Regulation of Notch Signaling by O-Linked Fucose
TLDR
The results indicate that OFUT1 is a core component of the Notch pathway, which is required for the activation of Notch by its ligands, and whose regulation may contribute to the pattern of notch activation during development. Expand
Roles of glycosylation in Notch signaling.
TLDR
Notch and the DSL Notch ligands Delta and Serrate/Jagged are glycoproteins with a single transmembrane domain which contains numerous epidermal growth factor-like repeats which are post-translationally modified by a variety of glycans. Expand
Protein O-fucosyltransferase 1 is an essential component of Notch signaling pathways
  • S. Shi, P. Stanley
  • Biology, Medicine
  • Proceedings of the National Academy of Sciences of the United States of America
  • 2003
TLDR
It is shown that mouse embryos lacking protein O-fucosyltransferase 1 die at midgestation with severe defects in somitogenesis, vasculogenesis, cardiogenesis, and neurogenesis, and the phenotype is similar to that of embryos lacking downstream effectors of all Notch signaling pathways such as presenilins or RBP-Jκ. Expand
An O-fucose site in the ligand binding domain inhibits Notch activation
TLDR
The results indicate that glycosylation of an EGF domain proposed to be essential for ligand binding, EGF12, is crucial to the inhibition of Serrate-to-Notch signaling by Fringe, and elimination of three other highly conserved sites of O-fucosylation does not have detectable effects. Expand
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References

SHOWING 1-10 OF 30 REFERENCES
Fringe modulates Notch–ligand interactions
The Notch family of transmembrane receptor proteins mediate developmental cell-fate decisions, and mutations in mammalian Notch genes have been implicated in leukaemia, breast cancer, stroke andExpand
Secreted Fringe-like Signaling Molecules May Be Glycosyltransferases
TLDR
Multiple functions have been assumed for a Xenopus homologue (lunatic Fringe, lFNG) including the induction of mesoderm; a complex expression pattern supports this notion. Expand
The Notch1 receptor is cleaved constitutively by a furin-like convertase.
TLDR
The results confirm and extend recent reports indicating that the Notch receptor exists at the plasma membrane as a heterodimeric molecule, but disagree as to the nature of the protease that is responsible for the cleavage that takes place in the extracellular region. Expand
A family of mammalian Fringe genes implicated in boundary determination and the Notch pathway.
The formation of boundaries between groups of cells is a universal feature of metazoan development. Drosophila fringe modulates the activation of the Notch signal transduction pathway at theExpand
Intracellular Cleavage of Notch Leads to a Heterodimeric Receptor on the Plasma Membrane
TLDR
Evidence is presented demonstrating that the Notch receptor on the plasma membrane is cleaved and two fragments are tethered together on the Plasma membrane by a link that is sensitive to reducing conditions, forming a heterodimeric receptor. Expand
Serrate-mediated activation of Notch is specifically blocked by the product of the gene fringe in the dorsal compartment of the Drosophila wing imaginal disc.
TLDR
It is demonstrated that Serrate, which is expressed in the dorsal compartment, does not signal in the lateral regions due to the action of the fringe gene product, and replacement of the N-terminal region of Serrate with the corresponding region of Delta abolishes the ability of fringe to regulate Serrate without altering Serrate-specific signaling. Expand
The Secreted Product of Xenopus Gene lunatic Fringe, a Vertebrate Signaling Molecule
TLDR
Results indicate that secreted lunatic Fringe can induce mesoderm and reveal that the Fringe proteins are a family of vertebrate signaling molecules. Expand
Fringe, Notch, and making developmental boundaries.
  • K. Irvine
  • Biology, Medicine
  • Current opinion in genetics & development
  • 1999
TLDR
Lunatic Fringe has been shown to be required for vertebrate somitogenesis, where it appears to act as a crucial link between a molecular clock and the regulation of Notch signaling. Expand
EphrinB Ligands Recruit GRIP Family PDZ Adaptor Proteins into Raft Membrane Microdomains
TLDR
These findings suggest that GRIP proteins provide a scaffold for the assembly of a multiprotein signaling complex downstream of ephrinB ligands. Expand
ELF-2, a new member of the Eph ligand family, is segmentally expressed in mouse embryos in the region of the hindbrain and newly forming somites
TLDR
A new member of the Eph ligand family is described, designated ELF-2, which shows closest homology to the other known transmembrane ligand in the family, ELK-L/LERK-2/Cek5-L, with 57% identity in the extracellular domain and striking homology in the cytoplasmic domain. Expand
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