SACCHAROMYCES-CEREVISIAE GPI10, THE FUNCTIONAL HOMOLOG OF HUMAN PIG-B, IS REQUIRED FOR GLYCOSYLPHOSPHATIDYLINOSITOL-ANCHOR SYNTHESIS

An increasing number of plasma membrane proteins have been shown to be attached to the membrane via a glycosylphosphatidylinositol (GPI) moi ety. All eukaryotes share a highly conserved GPI-core structure EthN-P -Man(3)-GlcN-PI, where EthN is ethanolamine. We have identified a prot ein encoded by the yeast open reading frame YGL142C that shares 33% id entity with the human Pig-B protein. Deletion of this essential gene l eads to a block in GPI anchor biosynthesis. We therefore named the gen e GPI10. Gpi10P and Pig-B are functional homologues and the lethal del etion of GPI10 can be rescued by expression of the PIG-B cDNA. As foun d for PIG-B mutant cells, gpi10 deletant cells cannot attach the third mannose in an alpha-1,2 linkage to the GPI core-structure intermediat e. Overexpression of GPI10 gives partial resistance to the GPI-synthes is inhibitor YW3548, suggesting that this gene product may affect the target of the inhibitor.