Type II platelet-activating factor-acetylhydrolase is essential for epithelial morphogenesis in Caenorhabditis elegans

doi:10.1073/pnas.0405507101

Type II platelet-activating factor-acetylhydrolase is essential for epithelial morphogenesis in Caenorhabditis elegans

^*Graduate School of Pharmaceutical Sciences and ^§Graduate School of Sciences, University of Tokyo, 7-3-1 Hongo, Bunkyo-ku, Tokyo 113-0033, Japan; ^‡RIKEN Center for Developmental Biology, Chuo-ku, Kobe, Hyogo 650-0047, Japan; ^†Laboratory of Cellular Biochemistry, RIKEN, 2-1, Hirosawa, Wako-shi, Saitama 351-0198, Japan; and ^¶Faculty of Pharmaceutical Sciences, Teikyo University, Sagamiko, Tsukui, Kanagawa 119-0195, Japan

Communicated by John A. Glomset, University of Washington, Seattle, WA, July 29, 2004 (received for review September 30, 2003)

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.

Footnotes

↵ ∥ To whom correspondence should be addressed. E-mail: harai{at}mol.f.u-tokyo.ac.jp.
Abbreviations: PAF, platelet-activating factor; PAF-AH, PAF-acetylhydrolase; PAF-AH (II), intracellular type II PAF-AH; RNAi, RNA interference.
Data deposition: The sequences reported in this paper have been deposited in the GenBank database (accession nos. AF386744 and AF386745).