Pre-Golgi Intermediates: Oligosaccharide Trimming and Protein Quality control

Abstract

Machinery components of the protein quality control such as chaperones, protein disulfide isomerase, lectins (calnexin and calreticulin), ERp57, glucosidase II, and glucosyltransferase are all functioning in the endoplasmic reticulum. The scheme depicts the major steps in the quality control of glycoprotein folding. Glycoproteins bearing monoglucosylated oligosaccharides either due to trimming by glucosidase II (Gls II) or through reglucosylation by glucosyltransferase (GT) will be bound by calnexin or calreticulin. Dissociation of such glycoprotein-lectin complexes will be achieved by glucosidase II, and correctly folded glycoproteins may be processed by ER-mannosidase I (ER Man I) and exported from the endoplasmic reticulum. However, not correctly folded glycoproteins will be recognized and reglucosylated by glucosyltransferase and enter a new calnexin/calreticulin cycle. Thus, the opposing actions of glucosidase II and glucosyltransferase provide the basis for the on-and-off-cycle. If correct folding cannot be achieved, trimming by ER-mannosidase I and II will be followed by interaction with EDEM 1 and OS9, respectively.