Selective Manipulation of Endoplasmic Reticulum Mannosidase Activities Using Inhibitor as Molecular Tool

Abstract

Glycoproteins are synthesized in the endoplasmic reticulum (ER). Glycan structures on the glycoprotein function as folding, secretion, and degradation signals. Especially in the sorting step of glycoproteins, mannose trimmings of Man₉GlcNAc₂ (M9) mediated by α1,2-mannosidases in the ER are involved in secretion and degradation. Several glycan isomers produced through the sorting process are assumed to be secretion and degradation signals. However, it is unclear whether these mannose trimmings occurred regioselectively or randomly. To answer this question, we found selective inhibitors of the production of secretion and degradation signals, respectively. With these selective inhibitors, mannose trimming pathway analysis was carried out. The pathway analysis results indicate that two independent mannose trimming pathways exist in the ER.