title: New members of the mammalian glycerophosphodiester phosphodiesterase family: GDE4 and GDE7 produce lysophosphatidic acid by lysophospholipase D activity.
abstract: The known mammalian glycerophosphodiester phosphodiesterases (GP-PDEs) hydrolyze glycerophosphodiesters. In this study, two novel members of the mammalian GP-PDE family, GDE4 and GDE7, were isolated, and the molecular basis of mammalian GP-PDEs was further explored. The GDE4 and GDE7 sequences are highly homologous and evolutionarily close. GDE4 is expressed in intestinal epithelial cells, spermatids, and macrophages, whereas GDE7 is particularly expressed in gastro-esophageal epithelial cells. Unlike other mammalian GP-PDEs, GDE4 and GDE7 cannot hydrolyze either glycerophosphoinositol or glycerophosphocholine. Unexpectedly, both GDE4 and GDE7 show a lysophospholipase D activity toward lysophosphatidylcholine (lyso-PC). We purified the recombinant GDE4 and GDE7 proteins and show that these enzymes can hydrolyze lyso-PC to produce lysophosphatidic acid (LPA). Further characterization of purified recombinant GDE4 showed that it can also convert lyso-platelet-activating factor (1-O-alkyl-sn-glycero-3-phosphocholine; lyso-PAF) to alkyl-LPA. These data contribute to our current understanding of mammalian GP-PDEs and of their physiological roles via the control of lyso-PC and lyso-PAF metabolism in gastrointestinal epithelial cells and macrophages.
authors.affiliation: From the Department of Biochemistry, Gunma University Graduate School of Medicine, Maebashi, Gunma 371-8511, Japan.
authors.forename: Noriyasu
authors.initials: N
authors.lastname: Ohshima
authors.affiliation: the Department of Molecular and Applied Bioscience, Graduate School of Biosphere Science, Hiroshima University, Higashi-Hiroshima City 739-8511, Japan, and.
authors.forename: Takahiro
authors.initials: T
authors.lastname: Kudo
authors.affiliation: the Department of Molecular and Applied Bioscience, Graduate School of Biosphere Science, Hiroshima University, Higashi-Hiroshima City 739-8511, Japan, and.
authors.forename: Yosuke
authors.initials: Y
authors.lastname: Yamashita
authors.affiliation: the Institute of Protein Biochemistry, National Research Council, 80131 Naples, Italy.
authors.forename: Stefania
authors.initials: S
authors.lastname: Mariggiò
authors.affiliation: From the Department of Biochemistry, Gunma University Graduate School of Medicine, Maebashi, Gunma 371-8511, Japan.
authors.forename: Mari
authors.initials: M
authors.lastname: Araki
authors.affiliation: the Department of Molecular and Applied Bioscience, Graduate School of Biosphere Science, Hiroshima University, Higashi-Hiroshima City 739-8511, Japan, and.
authors.forename: Ayako
authors.initials: A
authors.lastname: Honda
authors.affiliation: the Department of Molecular and Applied Bioscience, Graduate School of Biosphere Science, Hiroshima University, Higashi-Hiroshima City 739-8511, Japan, and.
authors.forename: Tomomi
authors.initials: T
authors.lastname: Nagano
authors.affiliation: From the Department of Biochemistry, Gunma University Graduate School of Medicine, Maebashi, Gunma 371-8511, Japan.
authors.forename: Chiaki
authors.initials: C
authors.lastname: Isaji
authors.affiliation: the Department of Molecular and Applied Bioscience, Graduate School of Biosphere Science, Hiroshima University, Higashi-Hiroshima City 739-8511, Japan, and.
authors.forename: Norihisa
authors.initials: N
authors.lastname: Kato
authors.affiliation: the Institute of Protein Biochemistry, National Research Council, 80131 Naples, Italy.
authors.forename: Daniela
authors.initials: D
authors.lastname: Corda
authors.affiliation: From the Department of Biochemistry, Gunma University Graduate School of Medicine, Maebashi, Gunma 371-8511, Japan.
authors.forename: Takashi
authors.initials: T
authors.lastname: Izumi
authors.affiliation: the Department of Molecular and Applied Bioscience, Graduate School of Biosphere Science, Hiroshima University, Higashi-Hiroshima City 739-8511, Japan, and yanaka@hiroshima-u.ac.jp.
authors.forename: Noriyuki
authors.initials: N
authors.lastname: Yanaka
mesh_terms: D000595:Amino Acid Sequence; D000818:Animals; D015153:Blotting, Western; D002478:Cells, Cultured; D017403:In Situ Hybridization; D008246:Lysophospholipids / Q000378:metabolism*; D008297:Male; D051379:Mice; D008813:Mice, Inbred ICR; D008820:Mice, Obese; D008856:Microscopy, Fluorescence; D008969:Molecular Sequence Data; D010727:Phosphoric Diester Hydrolases / Q000235:genetics / Q000378:metabolism*; D010802:Phylogeny; D010972:Platelet Activating Factor / Q000031:analogs & derivatives* / Q000378:metabolism; D012333:RNA, Messenger / Q000235:genetics; D060888:Real-Time Polymerase Chain Reaction; D011994:Recombinant Proteins / Q000235:genetics / Q000378:metabolism; D020133:Reverse Transcriptase Polymerase Chain Reaction; D017386:Sequence Homology, Amino Acid; D000099189:Lysophospholipase D
chemical_list: D008246:Lysophospholipids; D010727:Phosphoric Diester Hydrolases; D010972:Platelet Activating Factor; D012333:RNA, Messenger; D011994:Recombinant Proteins; D000099189:Lysophospholipase D; C029271:O-deacetyl platelet activating factor; C000597562:GDE4 protein, mouse; C000597563:GDE7 protein, mouse; C038133:glycerophosphodiester phosphodiesterase; C032881:lysophosphatidic acid
keywords: Enzyme; Enzyme Kinetics; Gene Amplification; Glycerophospholipid; Lysophospholipid; Phosphatidylcholine; Phospholipase D; Phospholipid; Phospholipid Metabolism