The B3GALTL gene encodes a beta-1,3-glucosyltransferase (β3Glc-T) that transfers glucose to O-linked fucosylglycans on thrombospondin type-1 repeats (TSRs) of several proteins. Protein O-linked fucosylation is unusual glycosylation associated with important biological functions such as Notch signaling. Two distinct fucosylation pathways synthesizing O-fucosylglycans have been reported on cysteine-knotted core proteins, namely, epidermal growth factor-like (EGF) repeats and TSRs (Fig. 3.1). O-fucosylation on the EGF repeats is catalyzed by POFUT1, which transfers Fuc toward Ser/Thr residues on specific core proteins, and followed by Fringe, which transfers GlcNAc toward Fuc and is essential for Notch activation through its ligands Delta and Serrate/Jagged. This modification is further elongated by reactions of β4GalT and α2,3 or α2,6 SiaT. Another O-fucosylglycan on TSRs is a unique disaccharide structure of Glcβ1,3Fucα1-Ser/Thr synthesized by POFUT2 for the first Fuc and β3Glc-T for the followed Glc, and further elongation has not been identified. Interestingly, O-fucosylation on TSRs occurs in ER, as opposed to that on the EGF repeat, which occurs in ER and the Golgi apparatus. Biological functions of disaccharide of Glcβ1,3Fucα1-TSRs are still remaining unknown; however, a mutation in B3GALTL causes Peters plus syndrome indicating that Glc modification on O-fuc of the TSRs is essential for their function.
KeywordsAcceptor Substrate Ligand Delta Glucosyltransferase Activity Microsomal Membrane Fraction Core Protein Structure
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