Sorting defects of the tryptophan permease Tat2 in an erg2 yeast mutant.
Cholesterol (ergosterol in yeast) in conjunction with sphingolipids forms tight-packing microdomains, 'lipid rafts,' which are thought to be critical for intracellular protein sorting in eukaryotic cells. When the activity of Erg9 involved in the first step of ergosterol biogenesis, but not that of Erg6 involved in a late step, is compromised, vacuolar degradation of the tryptophan permease Tat2 is promoted. It is unknown whether this difference simply reflects the difference between the inhibition of early and late steps. Here, it is shown that the deletion in ERG2, which encodes sterol C8-C7 isomerase (the next enzymatic step after Erg6), promotes the vacuolar degradation of Tat2. It suggests that the accumulation of specific sterol intermediates may alter lipid raft structures, promoting Tat2 degradation. The erg2Delta-mediated Tat2 degradation required Tat2 ubiquitination. Lipid raft association of Tat2 is compromised in erg2Delta cells. The erg2Delta mutation showed a synthetic growth defect with the trp1 mutation, indicating that Tat2 sorting is preferentially compromised in these mutants. Consistent with this notion, the raft-associated protein Pma1 was associated with detergent-resistant membranes and sorted to the plasma membrane. This study suggests the potential for the pharmacological control of cellular nutrient uptake in humans by regulating enzymes involved in cholesterol biogenesis.
Daicho
Katsue
K
Faculty of Science, Shizuoka University, Shizuoka, Japan.
Makino
Nishiho
N
Hiraki
Toshiki
T
Ueno
Masaru
M
Uritani
Masahiro
M
Abe
Fumiyoshi
F
Ushimaru
Takashi
T
D026905:Amino Acid Transport Systems / Q000378:metabolism*; D053898:Biosynthetic Pathways; D017353:Gene Deletion; D006801:Humans; D021381:Protein Transport; D012441:Saccharomyces cerevisiae / Q000235:genetics* / Q000378:metabolism*; D029701:Saccharomyces cerevisiae Proteins / Q000235:genetics* / Q000378:metabolism; D013251:Steroid Isomerases / Q000235:genetics*; D013261:Sterols / Q000096:biosynthesis; D054875:Ubiquitination
D026905:Amino Acid Transport Systems; D029701:Saccharomyces cerevisiae Proteins; D013261:Sterols; C429825:TAT2 protein, S cerevisiae; D013251:Steroid Isomerases; C022669:delta(8)-delta(7)-sterol isomerase