期刊
GENES TO CELLS
卷 17, 期 9, 页码 748-757出版社
WILEY
DOI: 10.1111/j.1365-2443.2012.01624.x
关键词
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资金
- National Center for Research Resources of the National Institutes of Health
- Core Research for Evolutional Science and Technology, Japan Science and Technology Agency (CREST, JST)
- Program for Promotion of Basic and Applied Researches for Innovations in Bio-oriented Industry
- Japanese Ministry of Education, Culture, Sports, Science, and Technology
- Japanese Ministry of Health, Labor, and Welfare
- Japan Society for the Promotion of Science for Young Scientists
Phosphatidylinositol (PI) is a constituent of biomembranes and a precursor of all phosphoinositides (PIPs). A prominent characteristic of PI is that its sn-2 position is highly enriched in polyunsaturated fatty acids (PUFAs), such as arachidonic acid or eicosapentaenoic acid. However, the biological significance of PUFA-containing PI remains unknown. We previously identified Caenorhabditis elegans (C. elegans) mboa-7 as an acyltransferase that incorporates PUFAs into the sn-2 position of PI. In this study, we performed an RNAi enhancer screen against PI kinases and phosphatases using mboa-7 mutants that have a reduced PUFA content in PI. Among the genes tested, knockdown of vps-34, a catalytic subunit of class III PI 3-kinase that produces PI 3-phosphate (PI3P) from PI, caused severe growth defects in mboa-7 mutants. In both vps-34 RNAi-treated wild-type worms and mboa-7 mutants, the size of PI3P-positive early endosomes was significantly decreased. We also performed an RNAi enhancer screen against PI3P-related genes and found that, like knockdown of vps-34, knockdown of autophagy-related genes caused severe growth defects in mboa-7 mutants. Finally, we showed that autophagic clearance of protein aggregates is impaired in mboa-7 mutants. Taken together, these results suggest that the PUFA chain in PI has a role in some PI3P signaling.
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