Mnl1p, an alpha -mannosidase-like protein in yeast Saccharomyces cerevisiae, is required for endoplasmic reticulum-associated degradation of glycoproteins

J Biol Chem. 2001 Mar 23;276(12):8635-8. doi: 10.1074/jbc.C100023200. Epub 2001 Jan 31.

Abstract

The endoplasmic reticulum (ER) has a mechanism to block the exit of misfolded or unassembled proteins from the ER for the downstream organelles in the secretory pathway. Misfolded proteins retained in the ER are subjected to proteasome-dependent degradation in the cytosol when they cannot achieve correct folding and/or assembly within an appropriate time window. Although specific mannose trimming of the protein-bound oligosaccharide is essential for the degradation of misfolded glycoproteins, the precise mechanism for this recognition remains obscure. Here we report a new alpha-mannosidase-like protein, Mnl1p (mannosidase-like protein), in the yeast ER. Mnl1p is unlikely to exhibit alpha1,2-mannosidase activity, because it lacks cysteine residues that are essential for alpha1,2-mannosidase. However deletion of the MNL1 gene causes retardation of the degradation of misfolded carboxypeptidase Y, but not of the unglycosylated mutant form of the yeast alpha-mating pheromone. Possible roles of Mnl1p in the degradation and in the ER-retention of misfolded glycoproteins are discussed.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Amino Acid Sequence
  • Endoplasmic Reticulum / metabolism*
  • Glycoproteins / metabolism*
  • Hydrolysis
  • Mannosidases / chemistry
  • Mannosidases / metabolism*
  • Molecular Sequence Data
  • Protein Folding
  • Saccharomyces cerevisiae / metabolism*
  • Saccharomyces cerevisiae Proteins*
  • Sequence Deletion
  • Sequence Homology, Amino Acid

Substances

  • Glycoproteins
  • Saccharomyces cerevisiae Proteins
  • MNL1 protein, S cerevisiae
  • Mannosidases