title: Depletion of mboa-7, an enzyme that incorporates polyunsaturated fatty acids into phosphatidylinositol (PI), impairs PI 3-phosphate signaling in Caenorhabditis elegans.
abstract: 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.affiliation: Graduate School of Pharmaceutical Sciences, University of Tokyo, Tokyo, 113-0033, Japan.
authors.forename: Hyeon-Cheol
authors.initials: HC
authors.lastname: Lee
authors.forename: Takuya
authors.initials: T
authors.lastname: Kubo
authors.forename: Nozomu
authors.initials: N
authors.lastname: Kono
authors.forename: Eriko
authors.initials: E
authors.lastname: Kage-Nakadai
authors.forename: Keiko
authors.initials: K
authors.lastname: Gengyo-Ando
authors.forename: Shohei
authors.initials: S
authors.lastname: Mitani
authors.forename: Takao
authors.initials: T
authors.lastname: Inoue
authors.forename: Hiroyuki
authors.initials: H
authors.lastname: Arai
mesh_terms: D000217:Acyltransferases / Q000235:genetics / Q000378:metabolism; D000483:Alleles; D000818:Animals; D030801:Animals, Genetically Modified / Q000235:genetics / Q000254:growth & development / Q000378:metabolism; D001343:Autophagy; D017173:Caenorhabditis elegans / Q000201:enzymology* / Q000235:genetics / Q000254:growth & development; D029742:Caenorhabditis elegans Proteins / Q000235:genetics / Q000378:metabolism*; D003001:Cloning, Molecular; D011992:Endosomes / Q000235:genetics / Q000378:metabolism; D005231:Fatty Acids, Unsaturated / Q000235:genetics / Q000378:metabolism*; D017353:Gene Deletion; D055785:Gene Knockdown Techniques; D005822:Genetic Vectors / Q000235:genetics / Q000378:metabolism; D019869:Phosphatidylinositol 3-Kinases / Q000235:genetics / Q000378:metabolism; D018129:Phosphatidylinositol Phosphates / Q000235:genetics / Q000378:metabolism*; D010716:Phosphatidylinositols / Q000378:metabolism*; D011401:Promoter Regions, Genetic; D034622:RNA Interference; D015398:Signal Transduction; D014960:X Chromosome / Q000235:genetics / Q000378:metabolism
chemical_list: D029742:Caenorhabditis elegans Proteins; D005231:Fatty Acids, Unsaturated; D018129:Phosphatidylinositol Phosphates; D010716:Phosphatidylinositols; C055525:phosphatidylinositol 3-phosphate; D000217:Acyltransferases; D019869:Phosphatidylinositol 3-Kinases