title: Regulated transcription of the Saccharomyces cerevisiae phosphatidylinositol biosynthetic gene, PIS1, yields pleiotropic effects on phospholipid synthesis.
abstract: Phosphatidylinositol is an important membrane lipid in Saccharomyces cerevisiae and other eukaryotes. Phosphatidylinositol and its metabolites (phosphoinositides, inositol polyphosphates, etc.) affect many cellular processes with implications in human diseases. Phosphatidylinositol synthesis in S. cerevisiae requires the essential PIS1 gene. Recent studies reveal that PIS1 expression is regulated at the level of transcription in response to carbon source, oxygen, and zinc. However, the consequence of this regulation on phosphatidylinositol levels and functions has not been thoroughly studied. To investigate this, we created a strain with a galactose-inducible GAL1-PIS1 gene. In this strain, the amount of phosphatidylinositol correlated with PIS1 expression but did not exceed c. 25% of the total phospholipid composition. Interestingly, we found that 4% phosphatidylinositol was sufficient for cell growth. We also found that reduced PIS1 expression yielded derepression of two phospholipid biosynthetic genes (INO1 and CHO1) and the INO2 regulatory gene. Consistent with this derepression, reduced PIS1 expression also yielded an overproduction of inositol (Opi(-)) phenotype. The effect on transcription of the INO1, CHO1, and INO2 genes is consistent with the accepted model that phosphatidic acid (PA) is the signal for regulation of these genes because decreased phosphatidylinositol synthesis would affect PA levels.
authors.affiliation: Department of Biological Sciences, Wayne State University, Detroit, MI, USA.
authors.forename: Niketa M
authors.initials: NM
authors.lastname: Jani
authors.forename: John M
authors.initials: JM
authors.lastname: Lopes
mesh_terms: D051792:Basic Helix-Loop-Helix Proteins / Q000096:biosynthesis; D010717:CDPdiacylglycerol-Serine O-Phosphatidyltransferase / Q000096:biosynthesis; D020869:Gene Expression Profiling; D015966:Gene Expression Regulation, Fungal; D006801:Humans; D007296:Myo-Inositol-1-Phosphate Synthase / Q000096:biosynthesis; D010712:Phosphatidic Acids / Q000378:metabolism; D010716:Phosphatidylinositols / Q000096:biosynthesis*; D012441:Saccharomyces cerevisiae / Q000235:genetics / Q000378:metabolism / Q000502:physiology*; D029701:Saccharomyces cerevisiae Proteins / Q000096:biosynthesis; D014158:Transcription, Genetic; D017855:Transferases (Other Substituted Phosphate Groups) / Q000096:biosynthesis* / Q000235:genetics
chemical_list: D051792:Basic Helix-Loop-Helix Proteins; D010717:CDPdiacylglycerol-Serine O-Phosphatidyltransferase; D007296:Myo-Inositol-1-Phosphate Synthase; D010712:Phosphatidic Acids; D010716:Phosphatidylinositols; D029701:Saccharomyces cerevisiae Proteins; D017855:Transferases (Other Substituted Phosphate Groups); C490519:CHO1 protein, S cerevisiae; C095723:INO2 protein, S cerevisiae; C478389:PIS1 protein, S cerevisiae; C519641:INO1 protein, S cerevisiae