Thesis or Dissertation A study on the effects of inositol depletion on the functions of phospholipid flippases in yeast

山神, 香菜子

In eukaryotic cells, type 4 P-type ATPases function as phospholipid flippases, whichtranslocate phospholipids from the exoplasmic leaflet to the cytoplasmic leaflet of the lipidbilayer. Flippases function in the formation of transport vesicles, but the mechanismremains unknown. Here, I isolate an arrestin-related trafficking adaptor, ART5, as amulticopy suppressor of the growth and endocytic recycling defects of flippase mutants inbudding yeast. Consistent with a previous report that Art5p downregulates the inositoltransporter Itr1p by endocytosis, I found that flippase mutations were also suppressed bythe disruption of ITR1, as well as by depletion of inositol from the culture medium.Interestingly, inositol depletion suppressed the defects in all five flippase mutants. Inositoldepletion also partially restored the formation of secretory vesicles in a flippase mutant.Inositol depletion caused changes in lipid composition, including a decrease inphosphatidylinositol and an increase in phosphatidylserine. A reduction inphosphatidylinositol levels caused by partially depleting the phosphatidylinositol synthasePis1p also suppressed a flippase mutation. These results suggest that inositol depletionchanges the lipid composition of the endosomal/TGN membranes, which results in vesicle2formation from these membranes in the absence of flippases.
Hokkaido University(北海道大学). 博士(生命科学)

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