TY - JOUR
T1 - Fatty acid-binding proteins interact with comparative gene identification-58 linking lipolysis with lipid ligand shuttling
AU - Hofer, Peter
AU - Boeszoermenyi, Andras
AU - Jaeger, Doris
AU - Feiler, Ursula
AU - Arthanari, Haribabu
AU - Mayer, Nicole
AU - Zehender, Fabian
AU - Rechberger, Gerald
AU - Oberer, Monika
AU - Zimmermann, Robert
AU - Lass, Achim
AU - Haemmerle, Guenter
AU - Breinbauer, Rolf
AU - Zechner, Rudolf
AU - Preiss-Landl, Karina
PY - 2015
Y1 - 2015
N2 - 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.
AB - 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.
UR - http://www.scopus.com/inward/record.url?eid=2-s2.0-84937876167&partnerID=MN8TOARS
U2 - 10.1074/jbc.M114.628958
DO - 10.1074/jbc.M114.628958
M3 - Article
SN - 1083-351X
VL - 290
SP - 18438
EP - 18453
JO - The Journal of Biological Chemistry
JF - The Journal of Biological Chemistry
ER -