Saccharomyces cerevisiae Ybr004c and its human homologue are required for addition of the second mannose during glycosylphosphatidylinositol precursor assembly

FEBS J. 2005 Mar;272(5):1160-8. doi: 10.1111/j.1742-4658.2005.04551.x.

Abstract

Addition of the second mannose is the only obvious step in glycosylphosphatidylinositol (GPI) precursor assembly for which a responsible gene has not been discovered. A bioinformatics-based strategy identified the essential Saccharomyces cerevisiae Ybr004c protein as a candidate for the second GPI alpha-mannosyltransferase (GPI-MT-II). S. cerevisiae cells depleted of Ybr004cp have weakened cell walls and abnormal morphology, are unable to incorporate [3H]inositol into proteins, and accumulate a GPI intermediate having a single mannose that is likely modified with ethanolamine phosphate. These data indicate that Ybr004cp-depleted yeast cells are defective in second mannose addition to GPIs, and suggest that Ybr004cp is GPI-MT-II or an essential subunit of that enzyme. Ybr004cp homologues are encoded in all sequenced eukaryotic genomes, and are predicted to have 8 transmembrane domains, but show no obvious resemblance to members of established glycosyltransferase families. The human Ybr004cp homologue can substitute for its S. cerevisiae counterpart in vivo.

Publication types

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

MeSH terms

  • Cell Survival
  • Databases as Topic
  • Glycosylphosphatidylinositols / metabolism*
  • Humans
  • Mannose / metabolism*
  • Mannosyltransferases / genetics
  • Mannosyltransferases / metabolism*
  • Molecular Sequence Data
  • Plasmids
  • Saccharomyces cerevisiae / genetics
  • Saccharomyces cerevisiae / metabolism*
  • Saccharomyces cerevisiae Proteins / genetics
  • Saccharomyces cerevisiae Proteins / metabolism*

Substances

  • Glycosylphosphatidylinositols
  • Saccharomyces cerevisiae Proteins
  • Mannosyltransferases
  • Mannose

Associated data

  • RefSeq/NP_060307