Role of UDP-Glucose:glycoprotein Glucosyltransferase in ER Glycoprotein Quality Control

CECILIA D'ALESSIO; ARMANDO J. PARODI

Glycoscience: Biology and Medicine

Springer Japan

Año: 2015; p. 913 - 920

The N-glycan-dependent quality control of glycoprotein folding prevents endoplasmic reticulum (ER) to Golgi exit of folding intermediates, irreparably misfolded glycoproteins and incompletely assembled multimeric complexes. It also enhances folding efficiency by preventing aggregation and facilitating formation of proper disulfide bonds. The control mechanism essentialy involves four components, resident lectin-chaperones (calnexin and calreticulin) that recognize monoglucosylated polymannose protein-linked glycans, a lectin-associated oxidoreductase acting on monoglucosylated glycoproteins (ERp57), a glucosyltransferase that creates monoglucosylated epitopes in protein-linked glycans (UGGT) and a glucosidase (GII) that removes the glucose units added by UGGT. This last enzyne is the only mechanism component sensing glycoprotein conformations as it creates monoglucosylated glycans exclusively in not properly folded glycoproteins or in not completely assembled multimeric glycoprotein complexes. The glucosidase is a heterodimer whose activity diminishes as ER mannosidases remove mannose units from N-glycans. This mini-review deals with our present knowledge on how the mechanism operates within the secretory pathway