Fatty acid-binding proteins interact with comparative gene identification-58 linking lipolysis with lipid ligand shuttling

Peter Hofer, Andras Boeszoermenyi, Doris Jaeger, Ursula Feiler, Haribabu Arthanari, Nicole Mayer, Fabian Zehender, Gerald Rechberger, Monika Oberer, Robert Zimmermann, Achim Lass, Guenter Haemmerle, Rolf Breinbauer, Rudolf Zechner, Karina Preiss-Landl

Research output: Contribution to journalArticle

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.
Original languageEnglish
Pages (from-to)18438-18453
JournalThe Journal of Biological Chemistry
Volume290
DOIs
Publication statusPublished - 2015

Fields of Expertise

  • Human- & Biotechnology

Treatment code (Nähere Zuordnung)

  • Experimental
  • Basic - Fundamental (Grundlagenforschung)

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    Hofer, P., Boeszoermenyi, A., Jaeger, D., Feiler, U., Arthanari, H., Mayer, N., ... Preiss-Landl, K. (2015). Fatty acid-binding proteins interact with comparative gene identification-58 linking lipolysis with lipid ligand shuttling. The Journal of Biological Chemistry, 290, 18438-18453. https://doi.org/10.1074/jbc.M114.628958