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- W2130204580 abstract "Abstract Valproic acid (VPA) is widely used to treat epilepsy and manic-depressive illness. Although VPA has been reported to exert a variety of biochemical effects, the exact mechanisms underlying its therapeutic effects remain elusive. To gain further insights into the molecular mechanisms of VPA action, a genetic screen for fission yeast mutants that show hypersensitivity to VPA was performed. One of the genes that we identified was vps45+, which encodes a member of the Sec1/Munc18 family that is implicated in membrane trafficking. Notably, several mutations affecting membrane trafficking also resulted in hypersensitivity to VPA. These include ypt3+ and ryh1+, both encoding a Rab family protein, and apm1+, encoding the μ1 subunit of the adaptor protein complex AP-1. More importantly, VPA caused vacuolar fragmentation and inhibited the glycosylation and the secretion of acid phosphatase in wild-type cells, suggesting that VPA affects membrane trafficking. Interestingly, the cell-wall-damaging agents such as micafungin or the inhibition of calcineurin dramatically enhanced the sensitivity of wild-type cells to VPA. Consistently, VPA treatment of wild-type cells enhanced their sensitivity to the cell-wall-digesting enzymes. Altogether, our results suggest that VPA affects membrane trafficking, which leads to the enhanced sensitivity to cell-wall damage in fission yeast." @default.
- W2130204580 created "2016-06-24" @default.
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- W2130204580 date "2007-04-01" @default.
- W2130204580 modified "2023-10-01" @default.
- W2130204580 title "Valproic Acid Affects Membrane Trafficking and Cell-Wall Integrity in Fission Yeast" @default.
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- W2130204580 doi "https://doi.org/10.1534/genetics.107.070946" @default.
- W2130204580 hasPubMedCentralId "https://www.ncbi.nlm.nih.gov/pmc/articles/1855103" @default.
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