| Generation of lysophosphatidylinositol by DDHD domain containing 1 (DDHD1): Possible involvement of phospholipase D/phosphatidic acid in the activation of DDHD1. | |
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MedLine Citation:
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PMID: 20359546 Owner: NLM Status: MEDLINE |
Abstract/OtherAbstract:
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GPR55 is a seven-transmembrane G-protein-coupled receptor that has been proposed as a novel type of cannabinoid receptor. Previously, we identified lysophosphatidylinositol (LPI), in particular 2-arachidonoyl-LPI, as an agonist for GPR55. In the present study, we examined whether intracellular phospholipase A1 (DDHD domain containing 1, or DDHD1), previously identified as phosphatidic acid (PA)-preferring PLA1 (PA-PLA1), is involved in the formation of 2-arachidonoyl-LPI. HEK293 cells expressing DDHD1 produced [(3)H]arachidonic acid-containing LPI after prelabeling with [(3)H]arachidonic acid and subsequent activation by ionomycin; the formation of [(3)H]LPI was inhibited by n-butanol and the overexpression of an inactive PLD1 mutant PLD1K898R. DDHD1 was translocated from the cytosol to membranes upon ionomycin treatment. A purified recombinant DDHD1 formed [(3)H]LPI when incubated with [(3)H]PI; the V(max) and apparent K(m) were 190 micromol/min/mg protein and 10 mol% PI, respectively. DDHD1 binds PA, and the addition of PA to DDHD1 increased the affinity for PI (K(m) ; 3 mol%) and augmented the PI-PLA1 activity. DDHD1 activated by PA was returned to a basal state by its own PA-hydrolytic activity. These results implicate DDHD1 in the formation of 2-arachidonoyl-LPI and indicate that the process is modulated by PA released by phospholipase D. Similar observations for the production of arachidonic acid-containing LPI in neuroblastoma cells suggest the DDHD1-LPI-GPR55 axis to be involved in functions in the brain. |
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Authors:
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Atsushi Yamashita; Tsukasa Kumazawa; Hiroki Koga; Naotaka Suzuki; Saori Oka; Takayuki Sugiura |
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Publication Detail:
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Type: Journal Article; Research Support, Non-U.S. Gov't Date: 2010-03-30 |
Journal Detail:
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Title: Biochimica et biophysica acta Volume: 1801 ISSN: 0006-3002 ISO Abbreviation: Biochim. Biophys. Acta Publication Date: 2010 Jul |
Date Detail:
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Created Date: 2010-05-31 Completed Date: 2010-07-20 Revised Date: - |
Medline Journal Info:
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Nlm Unique ID: 0217513 Medline TA: Biochim Biophys Acta Country: Netherlands |
Other Details:
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Languages: eng Pagination: 711-20 Citation Subset: IM |
Copyright Information:
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Copyright 2010 Elsevier B.V. All rights reserved. |
Affiliation:
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Faculty of Pharmaceutical Sciences, Teikyo University, Sagamiko, Sagamihara, Kanagawa 229-0195, Japan. ayamashi@pharm.teikyo-u.ac.jp |
Export Citation:
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| MeSH Terms | |
Descriptor/Qualifier:
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Brain
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metabolism Cell Line, Tumor Cell Membrane / enzymology Cytosol / enzymology Enzyme Activation / drug effects, genetics Humans Ionomycin / pharmacology Ionophores / pharmacology Lysophospholipids / genetics, metabolism* Mutation, Missense Phosphatidic Acids / genetics, metabolism* Phospholipase D / genetics, metabolism* Protein Transport / drug effects, genetics Receptors, G-Protein-Coupled / genetics, metabolism Recombinant Proteins / genetics, metabolism |
| Chemical | |
Reg. No./Substance:
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0/GPR55 protein, human; 0/Ionophores; 0/Lysophospholipids; 0/Phosphatidic Acids; 0/Receptors, G-Protein-Coupled; 0/Recombinant Proteins; 0/lysophosphatidylinositol; 56092-81-0/Ionomycin; EC 3.1.4.4/Phospholipase D |
From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine
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