合成3糖類が明かす小胞体マンノシダーゼ群のエンド結合識別能

Abstract

Glycans on the proteins in the endoplasmic reticulum (ER) act as signals of glycoprotein folding, secretion and degradation. Especially, secretion or degradation signals are produced by the action of ER mannosidases towards each branch of a tri-antennary (A-, B- and C-branch) Man9GlcNAc2 (M9) glycan. Thus, the resulting product after trimming reaction of M9 serves as different signals for determination of glycoprotein fate. Each branch of all terminal glycosidic linkages of M9 are α-1,2 type, while the adjacent inner glycosidic linkages are different. In this study, we examined whether ER mannosidases showed branch specificity by discriminating between different inner glycosides. For evaluation of the hypothesis, we synthesized four trisaccharides with different glycosidic linkages and applied to mannose trimming assays in the ER fraction derived from mouse liver. Through these assays, we report first experimental demonstration that α-1,2-mannosidases in the endoplasmic reticulum (ER) can discriminate inner glycosidic linkages of synthetic trisaccharides substrates.