Reference - Detail
|Author||Lee HC, Kubo T, Kono N, Kage-Nakadai E, Gengyo-Ando K, Mitani S, Inoue T, Arai H.|
|Title||Depletion of mboa-7, an enzyme that incorporates polyunsaturated fatty acids into phosphatidylinositol (PI), impairs PI 3-phosphate signaling in Caenorhabditis elegans.|
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.
|MeSH||Acyltransferases / genetics Acyltransferases / metabolism Alleles Animals Animals, Genetically Modified / genetics Animals, Genetically Modified / growth & development Animals, Genetically Modified / metabolism Autophagy Caenorhabditis elegans / enzymology* Caenorhabditis elegans / genetics Caenorhabditis elegans / growth & development Caenorhabditis elegans Proteins / genetics Caenorhabditis elegans Proteins / metabolism* Cloning, Molecular Endosomes / genetics Endosomes / metabolism Fatty Acids, Unsaturated / genetics Fatty Acids, Unsaturated / metabolism* Gene Deletion Gene Knockdown Techniques Genetic Vectors / genetics Genetic Vectors / metabolism Phosphatidylinositol 3-Kinases / genetics Phosphatidylinositol 3-Kinases / metabolism Phosphatidylinositol Phosphates / genetics Phosphatidylinositol Phosphates / metabolism* Phosphatidylinositols / metabolism* Promoter Regions, Genetic RNA Interference Signal Transduction* X Chromosome / genetics X Chromosome / metabolism|
|WOS Category||GENETICS & HEREDITY CELL BIOLOGY|