Modulation of receptor signaling by glycosylation: fringe is an O-fucose-beta1,3-N-acetylglucosaminyltransferase.
The Notch family of signaling receptors plays key roles in determining cell fate and growth control. Recently, a number of laboratories have shown that O-fucose glycans on the epidermal growth factor (EGF)-like repeats of the Notch extracellular domain modulate Notch signaling. Fringe, a known modifier of Notch function, is an O-fucose specific beta1,3-N-acetylglucosaminyltransferase. The transfer of GlcNAc to O-fucose on Notch by fringe results in the potentiation of signaling by the Delta class of Notch ligands, but causes inhibition of signaling by the Serrate/Jagged class of Notch ligands. Interestingly, addition of a beta1,4 galactose by beta4GalT-1 to the GlcNAc added by fringe is required for Jagged1-induced Notch signaling to be inhibited in a co-culture assay. Thus, both fringe and beta4GalT-1 are modulators of Notch function. Several models have been proposed to explain how alterations in O-fucose glycans result in changes in Notch signaling, and these models are discussed.
Haltiwanger
Robert S
RS
Department of Biochemistry and Cell Biology, Institute for Cell and Developmental Biology, State University of New York-Stony Brook, 11794-5215, USA. Robert.Haltiwanger@stonybrook.edu
Stanley
Pamela
P
D000818:Animals; D029721:Drosophila Proteins; D005643:Fucose / Q000378:metabolism; D006031:Glycosylation; D006801:Humans; D008565:Membrane Proteins / Q000378:metabolism*; D017351:N-Acetylglucosaminyltransferases / Q000378:metabolism*; D051880:Receptors, Notch; D015398:Signal Transduction / Q000502:physiology*
D029721:Drosophila Proteins; D008565:Membrane Proteins; D051880:Receptors, Notch; D005643:Fucose; D017351:N-Acetylglucosaminyltransferases; C024850:alpha-1,3-mannosyl-glycoprotein beta-1,2-N-acetylglucosaminyltransferase I; C090576:fng protein, Drosophila