Document Detail

Generation of lysophosphatidylinositol by DDHD domain containing 1 (DDHD1): Possible involvement of phospholipase D/phosphatidic acid in the activation of DDHD1.
MedLine Citation:
PMID:  20359546     Owner:  NLM     Status:  MEDLINE    
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.
Atsushi Yamashita; Tsukasa Kumazawa; Hiroki Koga; Naotaka Suzuki; Saori Oka; Takayuki Sugiura
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Publication Detail:
Type:  Journal Article; Research Support, Non-U.S. Gov't     Date:  2010-03-30
Journal Detail:
Title:  Biochimica et biophysica acta     Volume:  1801     ISSN:  0006-3002     ISO Abbreviation:  Biochim. Biophys. Acta     Publication Date:  2010 Jul 
Date Detail:
Created Date:  2010-05-31     Completed Date:  2010-07-20     Revised Date:  -    
Medline Journal Info:
Nlm Unique ID:  0217513     Medline TA:  Biochim Biophys Acta     Country:  Netherlands    
Other Details:
Languages:  eng     Pagination:  711-20     Citation Subset:  IM    
Copyright Information:
Copyright 2010 Elsevier B.V. All rights reserved.
Faculty of Pharmaceutical Sciences, Teikyo University, Sagamiko, Sagamihara, Kanagawa 229-0195, Japan.
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MeSH Terms
Brain / metabolism
Cell Line, Tumor
Cell Membrane / enzymology
Cytosol / enzymology
Enzyme Activation / drug effects,  genetics
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
Reg. No./Substance:
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 D

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