Role of the Yeast VAP Homolog, Scs2p, in INO1 Expression and Phospholipid Metabolism

Abstract

In the yeast Saccharomyces cerevisiae, the expression of phospholipid biosynthetic genes, including the INO1 gene (encoding inositol-l-phosphate synthase), is coordinately regulated by a cis-acting transcriptional element, UAS_INO (inositol-sensitive upstream activating sequence). For this paper we studied the effect of SCS2 disruption on INO1 expression. SCS2 encodes a type II membrane protein and its deletion leads to inositol auxotrophy at temperatures above 34°C. We found that the expression of the INO1 gene was reduced in the scs2Δ strain even when the cells were cultured under derepressing conditions for INO1 expression. However, the β-galactosidase gene fused with the INO1 promoter region was expressed normally in the scs2Δ strain. The phospholipid composition of scs2Δ cells was not dramatically changed compared with wild-type cells at 28°C, but the phosphatidylinositol level was reduced in scs2Δ cells cultured at 34°C. In addition, elevated phosphatidylcholine synthesis through the CDP-choline pathway was observed in the scs2Δ strain, and the disruption of genes involved in the CDP-choline pathway rescued the INO1 expression defect of the scs2Δ strain. These results indicate that Scs2p can contribute to coordinated phospholipid metabolism including INO1 expression by regulating phosphatidylcholine synthesis through the CDP-choline pathway.