The UDP-GLC: Glycoprotein Glucosyl Transferase and the Quality Control of Glycoprotein Folding in the Endoplasmic Reticulum

Abstract

This review deals with the stages of synthesis and processing of asparagine-linked oligosaccharides occurring in the lumen of the endoplasmic reticulum and their relation with the acquisition by glycoproteins of their proper tertiary structures. Special emphasis is put on reactions taking place in trypanosomatid protozoa as their study allowed detection of the transient glucosylation of glycoproteins, catalyzed by the UDP-Glc: glycoprotein glucosyltransferase and glucosidase II. The former enzyme has the unique property of covalently tagging not properly folded conformations by catalyzing the formation of protein-linked Glc₁Man₇GlcNAc₂, Glc₁Man₈GlcNac₂ and Glc₁Man₉GlcNA₂ from the unglucosylated compounds. The enzyme is a soluble protein of t that recognizes protein domains expohe endoplasmic reticulumsed in denatured but not in native conformations (probably hydrophobic amino acids) and the innermost N-acetylglucosamine unit that is hidden from macromolecular probes in most native glycoproteins. In vivo, the glucose units are removed by glucosidase II. The influence of oligosaccharides in glycoprotein folding is reviewed as well as the participation of endoplasmic reticulum chaperones (calnexin and calreticulin) that recognize monoglucosylated species in the same process. Glycoproteins that are not properly folded are retained in the endoplasmic reticulum where they are proteolytically degraded. A model for the quality control of glycoprotein folding in the endoplasmic reticulum in which calnexin (and calreticulin) and the UDP-Glc: glycoprotein glucosyltransferase are the main elements is reviewed.