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

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 GPl-GlcNAc transferase (GPl-GnT) complex in the ER, which catalyzes transfer of GlcNAc from UDP-GlcNAc to an acceptor phosphatidylinositol, the first step in the production of GPl-anchors for cell surface proteins. We also show that GTP bound Ras2 associates with the GPl-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 GPl-GnT. We propose that diminished GPl-anchor protein production contributes to hyperactive Ras phenotypes.