Modulation of receptor signaling by glycosylation:: fringe is an O-fucose-β1,3-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 beta4GaIT-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 beta4GaIT-1 are modulators of Notch function. Several models have been proposed to explain how alterations in O-facose glycans result in changes in Notch signaling, and these models are discussed. (C) 2002 Published by Elsevier Science B.V.