Yeast Ras regulates the complex that catalyzes the first step in GPI-anchor biosynthesis at the ER

Cell. 2004 May 28;117(5):637-48. doi: 10.1016/j.cell.2004.05.003.

Abstract

The yeast ERI1 gene encodes a small ER-localized protein that associates in vivo with GTP bound Ras2 in an effector loop-dependent manner. We showed previously that loss of Eri1 function results in hyperactive Ras phenotypes. Here, we demonstrate that Eri1 is a component of the GPI-GlcNAc transferase (GPI-GnT) complex in the ER, which catalyzes transfer of GlcNAc from UDP-GlcNAc to an acceptor phosphatidylinositol, the first step in the production of GPI-anchors for cell surface proteins. We also show that GTP bound Ras2 associates with the GPI-GnT complex in vivo and inhibits its activity, indicating that yeast Ras uses the ER as a signaling platform from which to negatively regulate the GPI-GnT. We propose that diminished GPI-anchor protein production contributes to hyperactive Ras phenotypes.

Publication types

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

MeSH terms

  • Carrier Proteins / genetics
  • Carrier Proteins / metabolism*
  • Cell Wall / metabolism
  • Chitin / metabolism
  • Endoplasmic Reticulum / metabolism*
  • Glycosylphosphatidylinositols / biosynthesis*
  • Guanosine Triphosphate / metabolism
  • Membrane Proteins / genetics
  • Membrane Proteins / metabolism
  • Mutation
  • Saccharomyces cerevisiae / metabolism
  • Saccharomyces cerevisiae Proteins / genetics
  • Saccharomyces cerevisiae Proteins / metabolism*
  • Signal Transduction
  • Uridine Diphosphate N-Acetylglucosamine / metabolism
  • ras Proteins / metabolism*

Substances

  • Carrier Proteins
  • Eri1 protein, S cerevisiae
  • GPI1 protein, S cerevisiae
  • Glycosylphosphatidylinositols
  • Membrane Proteins
  • Saccharomyces cerevisiae Proteins
  • Chitin
  • Uridine Diphosphate N-Acetylglucosamine
  • Guanosine Triphosphate
  • ras Proteins