title: Type II platelet-activating factor-acetylhydrolase is essential for epithelial morphogenesis in Caenorhabditis elegans.
abstract: Type II platelet-activating factor-acetylhydrolase [PAF-AH (II)] is an N-myristoylated enzyme that contains a lipase/esterase catalytic motif and selectively hydrolyzes the sn-2 acetyl ester of PAF and other short-chain acyl groups attached to phosphoglycerides. However, the physiological role of this enzyme remains to be elucidated. PAF-AH (II) is conserved in a variety of species ranging from a simple multicellular organism, Caenorhabditis elegans, to mammals. C. elegans possesses two homologous PAF-AH (II) genes, named paf-1 and paf-2. In this study, we generated these two loss-of-function mutants to elucidate the in vivo PAF-AH (II) function. Surprisingly, mutants of paf-2, a major isoform of C. elegans PAF-AH (II)s, exhibits gross defects in epithelial sheet formation, resulting in unsuccessful subsequent morphogenesis with complete penetrance. Moreover, paf-2 RNA interference worms show a variable abnormal morphology, including ectopic protrusions and a lumpy shape at the late embryonic and early larval stages due to epithelial organization defects. Consistent with these phenotypes, PAF-AH (II) is predominantly expressed in epithelial cells of C. elegans. This study demonstrates that PAF-AH (II) is essential for epithelial morphogenesis.
authors.affiliation: Graduate School of Pharmaceutical Sciences, University of Tokyo, 7-3-1 Hongo, Bunkyo-ku, Tokyo 113-0033, Japan.
authors.forename: Takao
authors.initials: T
authors.lastname: Inoue
authors.forename: Asako
authors.initials: A
authors.lastname: Sugimoto
authors.forename: Yuka
authors.initials: Y
authors.lastname: Suzuki
authors.forename: Masayuki
authors.initials: M
authors.lastname: Yamamoto
authors.forename: Masafumi
authors.initials: M
authors.lastname: Tsujimoto
authors.forename: Keizo
authors.initials: K
authors.lastname: Inoue
authors.forename: Junken
authors.initials: J
authors.lastname: Aoki
authors.forename: Hiroyuki
authors.initials: H
authors.lastname: Arai
mesh_terms: D043203:1-Alkyl-2-acetylglycerophosphocholine Esterase / Q000235:genetics / Q000502:physiology*; D000595:Amino Acid Sequence; D000818:Animals; D017173:Caenorhabditis elegans / Q000196:embryology* / Q000201:enzymology*; D004817:Epidermis / Q000196:embryology; D004848:Epithelium / Q000196:embryology; D008969:Molecular Sequence Data; D009024:Morphogenesis; D034622:RNA Interference
chemical_list: D043203:1-Alkyl-2-acetylglycerophosphocholine Esterase