Selective Manipulation of Discrete Mannosidase Activities in the Endoplasmic Reticulum by Using Reciprocally Selective Inhibitors

摘要: Within the endoplasmic reticulum, immature glycoproteins are sorted into secretion and degradation pathways through sequential trimming of mannose residues from Man9GlcNAc2 to Man5GlcNAc2 by combined actions assorted α-1,2-mannosidases. It has been speculated that specific glycoforms encode signals for degradation. However, it is unclear whether signal produced random mannosidase action or regioselectively in a sequenced manner Here, we report identification set selective inhibitors development conditions their use enable production distinct pools Man8GlcNAc2 isomers structurally defined synthetic substrate an reticulum fraction. Glycan processing analysis with these provides first biochemical evidence contributing traffic control glycoprotein quality control.