title: Fatty Acid-binding Proteins Interact with Comparative Gene Identification-58 Linking Lipolysis with Lipid Ligand Shuttling.
abstract: The coordinated breakdown of intracellular triglyceride (TG) stores requires the exquisitely regulated interaction of lipolytic enzymes with regulatory, accessory, and scaffolding proteins. Together they form a dynamic multiprotein network designated as the "lipolysome." Adipose triglyceride lipase (Atgl) catalyzes the initiating step of TG hydrolysis and requires comparative gene identification-58 (Cgi-58) as a potent activator of enzyme activity. Here, we identify adipocyte-type fatty acid-binding protein (A-Fabp) and other members of the fatty acid-binding protein (Fabp) family as interaction partners of Cgi-58. Co-immunoprecipitation, microscale thermophoresis, and solid phase assays proved direct protein/protein interaction between A-Fabp and Cgi-58. Using nuclear magnetic resonance titration experiments and site-directed mutagenesis, we located a potential contact region on A-Fabp. In functional terms, A-Fabp stimulates Atgl-catalyzed TG hydrolysis in a Cgi-58-dependent manner. Additionally, transcriptional transactivation assays with a luciferase reporter system revealed that Fabps enhance the ability of Atgl/Cgi-58-mediated lipolysis to induce the activity of peroxisome proliferator-activated receptors. Our studies identify Fabps as crucial structural and functional components of the lipolysome.
authors.affiliation: From the Institute of Molecular Biosciences, University of Graz, NAWI Graz, 8010 Graz, Austria.
authors.forename: Peter
authors.initials: P
authors.lastname: Hofer
authors.affiliation: From the Institute of Molecular Biosciences, University of Graz, NAWI Graz, 8010 Graz, Austria.
authors.forename: Andras
authors.initials: A
authors.lastname: Boeszoermenyi
authors.affiliation: From the Institute of Molecular Biosciences, University of Graz, NAWI Graz, 8010 Graz, Austria.
authors.forename: Doris
authors.initials: D
authors.lastname: Jaeger
authors.affiliation: From the Institute of Molecular Biosciences, University of Graz, NAWI Graz, 8010 Graz, Austria.
authors.forename: Ursula
authors.initials: U
authors.lastname: Feiler
authors.affiliation: the Department of Biological Chemistry and Molecular Pharmacology, Harvard Medical School, Boston, Massachusetts 02115.
authors.forename: Haribabu
authors.initials: H
authors.lastname: Arthanari
authors.affiliation: the Institute of Organic Chemistry, Graz University of Technology, 8010 Graz, Austria, and.
authors.forename: Nicole
authors.initials: N
authors.lastname: Mayer
authors.affiliation: the NanoTemper Technologies GmbH, 81369 Munich, Germany.
authors.forename: Fabian
authors.initials: F
authors.lastname: Zehender
authors.affiliation: From the Institute of Molecular Biosciences, University of Graz, NAWI Graz, 8010 Graz, Austria.
authors.forename: Gerald
authors.initials: G
authors.lastname: Rechberger
authors.affiliation: From the Institute of Molecular Biosciences, University of Graz, NAWI Graz, 8010 Graz, Austria.
authors.forename: Monika
authors.initials: M
authors.lastname: Oberer
authors.affiliation: From the Institute of Molecular Biosciences, University of Graz, NAWI Graz, 8010 Graz, Austria.
authors.forename: Robert
authors.initials: R
authors.lastname: Zimmermann
authors.affiliation: From the Institute of Molecular Biosciences, University of Graz, NAWI Graz, 8010 Graz, Austria.
authors.forename: Achim
authors.initials: A
authors.lastname: Lass
authors.affiliation: From the Institute of Molecular Biosciences, University of Graz, NAWI Graz, 8010 Graz, Austria.
authors.forename: Guenter
authors.initials: G
authors.lastname: Haemmerle
authors.affiliation: the Institute of Organic Chemistry, Graz University of Technology, 8010 Graz, Austria, and.
authors.forename: Rolf
authors.initials: R
authors.lastname: Breinbauer
authors.affiliation: From the Institute of Molecular Biosciences, University of Graz, NAWI Graz, 8010 Graz, Austria, rudolf.zechner@uni-graz.at.
authors.forename: Rudolf
authors.initials: R
authors.lastname: Zechner
authors.affiliation: From the Institute of Molecular Biosciences, University of Graz, NAWI Graz, 8010 Graz, Austria, karina.landl@uni-graz.at.
authors.forename: Karina
authors.initials: K
authors.lastname: Preiss-Landl
mesh_terms: D051103:1-Acylglycerol-3-Phosphate O-Acyltransferase / Q000235:genetics / Q000378:metabolism*; D000273:Adipose Tissue / Q000378:metabolism; D000818:Animals; D019556:COS Cells; D002522:Chlorocebus aethiops; D050556:Fatty Acid-Binding Proteins / Q000235:genetics / Q000378:metabolism*; D006801:Humans; D008024:Ligands; D008049:Lipase / Q000235:genetics / Q000378:metabolism*; D008066:Lipolysis / Q000235:genetics; D008081:Liposomes / Q000378:metabolism; D051379:Mice; D046912:Multiprotein Complexes / Q000235:genetics / Q000378:metabolism*; D047492:Peroxisome Proliferator-Activated Receptors / Q000378:metabolism; D059748:Proteolysis; D014280:Triglycerides / Q000378:metabolism*; D000217:Acyltransferases
chemical_list: D051103:1-Acylglycerol-3-Phosphate O-Acyltransferase; D050556:Fatty Acid-Binding Proteins; D008024:Ligands; D008049:Lipase; D008081:Liposomes; D046912:Multiprotein Complexes; D047492:Peroxisome Proliferator-Activated Receptors; D014280:Triglycerides; C493410:FABP4 protein, human; C492986:Abhd5 protein, mouse; C494445:PNPLA2 protein, mouse; D000217:Acyltransferases
keywords: adipose triglyceride lipase (Atgl); fatty acid-binding protein; lipid signaling; lipolysis; peroxisome proliferator-activated receptor (Ppar)