Metabolism and transportation pathways of GDP-fucose that are required for the O-fucosylation of Notch.

Notch is a single-pass transmembrane receptor that mediates the local cell-cell interactions necessary for many cell-fate decisions. The extra cellular domain of Notch contains a tandem array of epidermal growth factor-like (EGF-like) repeats. Some of these EGF-like repeats are O-fucosylated by protein O-fucosyltransferase 1 (O-fut1), which is essential for Notch signaling in Drosophila and mouse. This O-fucose is further modified by Fringe, a GlcNAc transferase and other glycosyltransferases (O-fut1 in Drosophila and Pofut1 in mouse), to form an O-linked tetrasaccharide, which modulates Notch's selective binding to its ligands.