Journal
JOURNAL OF CELL BIOLOGY
Volume 156, Issue 6, Pages 1015-1028Publisher
ROCKEFELLER UNIV PRESS
DOI: 10.1083/jcb.200201002
Keywords
VAC14; FAB1; PtdIns(3,5)P-2; vacuole; phosphatidylinositol
Categories
Funding
- NIA NIH HHS [T32 AG000214, T32 AG00214] Funding Source: Medline
- NIGMS NIH HHS [R01 GM050403, GM50403, F31 GM018506, 1 F31 GM8506-01] Funding Source: Medline
Ask authors/readers for more resources
Phosphatidylinositol 3,5-bisphosphate (PtdIns[3,5]P-2) was first identified as a nonabundant phospholipid whose levels increase in response to osmotic stress. In yeast, Fab1p catalyzes formation of PtdIns(3,5)P-2 via phosphorylation of Ptdlns(3)P. We have identified Vac14p, a novel vacuolar protein that regulates Ptdlns(3,5)P-2 synthesis by modulating Fab1p activity in both the absence and presence of osmotic stress. We find that Ptdlns(3)P levels are also elevated in response to osmotic stress, yet, only the elevation of Ptdlns(3,5)P-2 levels are regulated by Vac14p. Under basal conditions the levels of PtdIns(35)P-2 are 18-28-fold lower than the levels of PtdIns(3)P, Ptdlns(4)P, and Ptdlns(4,5)P-2. After a 10 min exposure to hyperosmotic stress the levels of PtdIns(3,5)P-2 rise 20-fold, bringing it to a cellular concentration that is similar to the other phosphoinositides. This suggests that PtdIns(3,5)P-2 plays a major role in osmotic stress, perhaps via regulation of vacuolar volume. In fact, during hyperosmotic stress the vacuole morphology of wild-type cells changes dramatically, to smaller, more highly fragmented vacuoles, whereas mutants unable to synthesize PtdIns(3,5)P-2 continue to maintain a single large vacuole. These findings demonstrate that Vac14p regulates the levels of PtdIns(3,5)P-2 and provide insight into why PtdIns(3,5)P-2 levels rise in response to osmotic stress.
Authors
I am an author on this paper
Click your name to claim this paper and add it to your profile.
Reviews
Recommended
No Data Available