title: A lysophospholipid acyltransferase antagonist, CI-976, creates novel membrane tubules marked by intracellular phospholipase A1 KIAA0725p.
abstract: CI-976 is a lysophospholipid acyltransferase antagonist that is known to affect secretory and endocytic membrane-trafficking pathways likely by increasing the lysophospholipid content in membranes. Our previous study suggested that lysophospholipids formed through the action of an intracellular phospholipase A(1), KIAA0725p (also known as DDHD2 and iPLA(1)γ), may be important for the association of this enzyme with membranes. In this study, we examined the effect of CI-976 on the membrane association of KIAA0725p. While in HeLa cells KIAA0725p is localized in the Golgi and cytosol, in mouse embryonic fibroblasts (MEFs), it was found to be principally localized in the cytosol with some on post-endoplasmic reticulum compartments including the cis-Golgi. Treatment of MEFs with CI-976 induced the redistribution of KIAA0725p to membrane tubules, which were in vicinity to fragmented mitochondria. These tubules were not decorated with canonical organelle markers including Golgi proteins. A human KIAA0725p mutant, which exhibits decreased membrane-binding ability, was also redistributed to membrane structures upon CI-976 treatment. Our data suggest that the association of KIAA0725p with membranes is regulated by lipid metabolism, and that CI-976 may create unique membrane structures that can be marked by KIAA0725p.
authors: School of Life Sciences, Tokyo University of Pharmacy and Life Sciences, Hachioji, Tokyo, Japan.
authors: Takashi
authors: T
authors: Baba
authors: Akitsugu
authors: A
authors: Yamamoto
authors: Mitsuo
authors: M
authors: Tagaya
authors: Katsuko
authors: K
authors: Tani
mesh_terms: D000813:Anilides / Q000494:pharmacology*; D000818:Animals; D002462:Cell Membrane / Q000187:drug effects* / Q000378:metabolism / Q000648:ultrastructure; D021961:Cell Membrane Structures / Q000187:drug effects / Q000378:metabolism / Q000648:ultrastructure; D003600:Cytosol / Q000187:drug effects / Q000378:metabolism; D000072159:Dynactin Complex; D004398:Dyneins / Q000378:metabolism; D004791:Enzyme Inhibitors / Q000494:pharmacology*; D005347:Fibroblasts / Q000187:drug effects / Q000378:metabolism; D006056:Golgi Apparatus / Q000187:drug effects / Q000378:metabolism; D006367:HeLa Cells / Q000187:drug effects; D006801:Humans; D006913:Hydroxysteroid Dehydrogenases / Q000378:metabolism; D007425:Intracellular Membranes / Q000201:enzymology; D051379:Mice; D008869:Microtubule-Associated Proteins / Q000378:metabolism; D009154:Mutation; D010740:Phospholipases / Q000235:genetics / Q000378:metabolism*; D054466:Phospholipases A1 / Q000378:metabolism; D002785:Sterol O-Acyltransferase / Q000037:antagonists & inhibitors*; D045002:3-alpha-Hydroxysteroid Dehydrogenase (B-Specific)
chemical_list: D000813:Anilides; D000072159:Dynactin Complex; D004398:Dyneins; D004791:Enzyme Inhibitors; D006913:Hydroxysteroid Dehydrogenases; D008869:Microtubule-Associated Proteins; D010740:Phospholipases; D054466:Phospholipases A1; D002785:Sterol O-Acyltransferase; C069304:PD 128042; C435496:AKR1C2 protein, human; D045002:3-alpha-Hydroxysteroid Dehydrogenase (B-Specific); C583713:DDHD2 protein, mouse; C541017:DDHD2 protein, human
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