Reglucosylation of glycoproteins and quality control of glycoprotein folding in the endoplasmic reticulum of yeast cells

Biochim Biophys Acta. 1999 Jan 6;1426(2):287-95. doi: 10.1016/s0304-4165(98)00130-5.

Abstract

Proteins entering the secretory pathway may be glycosylated upon transfer of an oligosaccharide (Glc3Man9GlcNAc2) from a dolichol-P-P derivative to nascent polypeptide chains in the lumen of the endoplasmic reticulum (ER). Oligosaccharides are then deglucosylated by glucosidases I and II (GII). Also in the ER, glycoproteins acquire their final tertiary structures, and species that fail to fold properly are retained and eventually degraded in the proteasome. It has been proposed that in mammalian cells the monoglucosylated oligosaccharides generated either by partial deglucosylation of the transferred compound or by reglucosylation of glucose-free oligosaccharides by the UDP-Glc:glycoprotein glucosyltransferase (GT) are recognized by ER resident lectins (calnexin and/or calreticulin). GT is a sensor of glycoprotein conformation as it only glucosylates misfolded species. The lectin-monoglucosylated oligosaccharide interaction would retain glycoproteins in the ER until correctly folded, and also facilitate their acquisition of proper tertiary structures by preventing aggregation. GII would liberate glycoproteins from the calnexin/calreticulin anchor, but species not properly folded would be reglucosylated by GT, and so continue to be retained by the lectins. Only when the protein becomes properly folded would it cease to be retained by the lectins. This review presents evidence suggesting that a similar quality control mechanism of glycoprotein folding is operative in Schizosaccharomyces pombe and that the mechanism in Saccharomyces cerevisiae probably differs substantially from that occurring in mammalian and Sch. pombe cells.

Publication types

  • Comparative Study
  • Research Support, Non-U.S. Gov't
  • Research Support, U.S. Gov't, P.H.S.
  • Review

MeSH terms

  • Animals
  • Carbohydrate Sequence
  • Endoplasmic Reticulum / metabolism
  • Glucosyltransferases / metabolism
  • Glycoproteins / biosynthesis*
  • Glycoproteins / chemistry
  • Molecular Sequence Data
  • Oligosaccharides / metabolism
  • Peptides / metabolism
  • Protein Folding
  • Quality Control
  • Yeasts / metabolism*
  • Yeasts / ultrastructure

Substances

  • Glycoproteins
  • Oligosaccharides
  • Peptides
  • Glucosyltransferases
  • alpha-1,4-glucan-protein synthase (UDP-forming)