THE YEAST SPT14 GENE IS HOMOLOGOUS TO THE HUMAN PIG-A GENE AND IS REQUIRED FOR GPI ANCHOR SYNTHESIS

The protein encoded by the yeast gene SPT14 shows high sequence simila rity to the human protein, PIG-A, whose loss of activity is at the ori gin of the disease paroxysmal nocturnal hemoglobinuria. The symptoms o f this disease are apparently due to a loss of cell surface, glycosylp hosphatidylinositol (GPI)-anchored proteins. Like PIG-A mutant cells, spt14 mutant cells are defective in GPI anchoring due to a defect in t he synthesis of GlcNAc-PI, the first step of GPI synthesis. The spt14 mutant causes several other abnormalities including transcriptional de fects and a downregulation of inositolphosphoceramide synthesis. We su ggest that these defects are indirect results of the loss of GPI ancho ring.