Transmembrane movement of dolichol linked carbohydrates during N-glycoprotein biosynthesis in the endoplasmic reticulum.

Abstract

The process of N-linked glycosylation of secretory proteins is characterized by enzymatic reactions occurring on both sides of the endoplasmic reticulum (ER) membrane. On either side multiple glycosyltransferases participate in the stepwise addition of monosaccharides to core oligosaccharide unit that is attached to the lipid carrier dolichyl pyrophosphate. Cytoplasm-oriented glycosyltransferases use nucleotide-activated sugars as substrates, whereas lumen-oriented transferases that act later in the pathway make use of dolichyl phosphate-linked monosaccharides. The completely assembled core oligosaccharide is transferred to proteins on the lumenal side of the ER. The topological organization of this biosynthetic pathway requires the translocation of lipid-linked mono- and oligo-saccharides across the ER membrane. The transfer of the substrates and intermediates depend on specific translocators, i.e. so called flippases.