THE YEAST BSD2-1 MUTATION INFLUENCES BOTH THE REQUIREMENT FOR PHOSPHATIDYLINOSITOL TRANSFER PROTEIN FUNCTION AND DEREPRESSION OF PHOSPHOLIPID BIOSYNTHETIC GENE-EXPRESSION IN YEAST

The BSD2-1 allele renders Saccharomyces cerevisiae independent of its normally essential requirement for phosphatidylinositol transfer prote in (Sec14p) in the stimulation of Golgi secretory function and cell vi ability. We now report that BSD2-1 yeast mutants also exhibit yet anot her phenotype, an inositol auxotrophy. We demonstrate that the basis f or this Ino(-) phenotype is the inability of BSD2-1 strains to derepre ss transcription of lNO1, the structural gene for the enzyme that cata lyzes the committed step in de novo inositol biosynthesis in yeast. Th is constitutive repression of INO1 expression is mediated through spec ific inactivation of Ino2p, a factor required for trans-activation of INO1 transcription, and we show that these transcriptional regulatory defects can be uncoupled from the ''bypass Sec14p'' phenotype of BSD2- 1 strains. Finally, we present evidence that newly synthesized phospha tidylinositol is subject to accelerated turnover in BSD2-1 mutants and that prevention of this accelerated phosphatidylinositol turnover in turn negates suppression of Sec14p defects by BSD2-1. We propose that, in BSD2-1 strains, a product(s) generated by phosphatidylinositol tur nover coordinately modulates the activities of both the Sec14p/Golgi p athway and the pathway through which transcription of phospholipid bio synthetic genes is derepressed.