The ergosterol biosynthesis inhibitor zaragozic acid promotes vacuolar degradation of the tryptophan permease Tat2p in yeast.
Ergosterol is the yeast functional equivalent of cholesterol in mammalian cells. Deletion of the ERG6 gene, which encodes an enzyme catalyzing a late step of ergosterol biosynthesis, impedes targeting of the tryptophan permease Tat2p to the plasma membrane, but does not promote vacuolar degradation. It is unknown whether similar features appear when other steps of ergosterol biogenesis are inhibited. We show herein that the ergosterol biosynthesis inhibitor zaragozic acid (ZA) evoked massive vacuolar degradation of Tat2p, accompanied by a decrease in tryptophan uptake. ZA inhibits squalene synthetase (SQS, EC 2.5.1.21), which catalyzes the first committed step in the formation of cholesterol/ergosterol. The degradation of Tat2p was dependent on the Rsp5p-mediated ubiquitination of Tat2p and was not suppressed by deletions of VPS1, VPS27, VPS45 or PEP12. We will discuss ZA-mediated Tat2p degradation in the context of lipid rafts.
Daicho
Katsue
K
Faculty of Science, Shizuoka University, Shizuoka 422-8529, Japan.
Maruyama
Hironori
H
Suzuki
Asuka
A
Ueno
Masaru
M
Uritani
Masahiro
M
Ushimaru
Takashi
T
D026905:Amino Acid Transport Systems / Q000378:metabolism*; D019086:Bridged Bicyclo Compounds, Heterocyclic / Q000494:pharmacology*; D056827:Endosomal Sorting Complexes Required for Transport; D004875:Ergosterol / Q000037:antagonists & inhibitors; D013186:Farnesyl-Diphosphate Farnesyltransferase / Q000037:antagonists & inhibitors; D008954:Models, Biological; D021381:Protein Transport / Q000502:physiology; D012441:Saccharomyces cerevisiae / Q000187:drug effects / Q000235:genetics / Q000378:metabolism*; D029701:Saccharomyces cerevisiae Proteins / Q000378:metabolism* / Q000502:physiology; D014233:Tricarboxylic Acids / Q000494:pharmacology*; D014364:Tryptophan / Q000378:metabolism; D043743:Ubiquitin-Protein Ligase Complexes / Q000378:metabolism; D014617:Vacuoles / Q000378:metabolism*; D033921:Vesicular Transport Proteins / Q000502:physiology
D026905:Amino Acid Transport Systems; D019086:Bridged Bicyclo Compounds, Heterocyclic; D056827:Endosomal Sorting Complexes Required for Transport; D029701:Saccharomyces cerevisiae Proteins; C429825:TAT2 protein, S cerevisiae; D014233:Tricarboxylic Acids; C119627:VPS27 protein, S cerevisiae; C092934:VPS45 protein, S cerevisiae; D033921:Vesicular Transport Proteins; C075117:squalestatin 1; D014364:Tryptophan; D043743:Ubiquitin-Protein Ligase Complexes; D013186:Farnesyl-Diphosphate Farnesyltransferase; C469287:RSP5 protein, S cerevisiae; D004875:Ergosterol