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Depletion of mboa-7, an enzyme that incorporates polyunsaturated fatty acids into phosphatidylinositol (PI), impairs PI 3-phosphate signaling in Caenorhabditis elegans.
MedLine Citation:
PMID:  22862955     Owner:  NLM     Status:  Publisher    
Abstract/OtherAbstract:
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.
Authors:
Hyeon-Cheol Lee; Takuya Kubo; Nozomu Kono; Eriko Kage-Nakadai; Keiko Gengyo-Ando; Shohei Mitani; Takao Inoue; Hiroyuki Arai
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Publication Detail:
Type:  JOURNAL ARTICLE     Date:  2012-8-1
Journal Detail:
Title:  Genes to cells : devoted to molecular & cellular mechanisms     Volume:  -     ISSN:  1365-2443     ISO Abbreviation:  Genes Cells     Publication Date:  2012 Aug 
Date Detail:
Created Date:  2012-8-6     Completed Date:  -     Revised Date:  -    
Medline Journal Info:
Nlm Unique ID:  9607379     Medline TA:  Genes Cells     Country:  -    
Other Details:
Languages:  ENG     Pagination:  -     Citation Subset:  -    
Copyright Information:
© 2012 The Authors Journal compilation © 2012 by the Molecular Biology Society of Japan/Blackwell Publishing Ltd.
Affiliation:
Graduate School of Pharmaceutical Sciences, University of Tokyo, Tokyo, 113-0033, Japan.
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