title: Optic atrophy 1 is an A-kinase anchoring protein on lipid droplets that mediates adrenergic control of lipolysis.
abstract: Adrenergic stimulation of adipocytes yields a cAMP signal that activates protein kinase A (PKA). PKA phosphorylates perilipin, a protein localized on the surface of lipid droplets that serves as a gatekeeper to regulate access of lipases converting stored triglycerides to free fatty acids and glycerol in a phosphorylation-dependent manner. Here, we report a new function for optic atrophy 1 (OPA1), a protein known to regulate mitochondrial dynamics, as a dual-specificity A-kinase anchoring protein associated with lipid droplets. By a variety of protein interaction assays, immunoprecipitation and immunolocalization experiments, we show that OPA1 organizes a supramolecular complex containing both PKA and perilipin. Furthermore, by a combination of siRNA-mediated knockdown, reconstitution experiments using full-length OPA1 with or without the ability to bind PKA or truncated OPA1 fused to a lipid droplet targeting domain and cellular delivery of PKA anchoring disruptor peptides, we demonstrate that OPA1 targeting of PKA to lipid droplets is necessary for hormonal control of perilipin phosphorylation and lipolysis.
authors: Centre for Molecular Medicine Norway, Nordic EMBL Partnership, University of Oslo, Oslo, Norway.
authors: Guillaume
authors: G
authors: Pidoux
authors: Oliwia
authors: O
authors: Witczak
authors: Elisabeth
authors: E
authors: Jarnæss
authors: Linda
authors: L
authors: Myrvold
authors: Henning
authors: H
authors: Urlaub
authors: Anne Jorunn
authors: AJ
authors: Stokka
authors: Thomas
authors: T
authors: Küntziger
authors: Kjetil
authors: K
authors: Taskén
mesh_terms: D041721:3T3-L1 Cells; D054758:A Kinase Anchor Proteins / Q000235:genetics / Q000378:metabolism / Q000502:physiology; D000318:Adrenergic beta-Agonists / Q000494:pharmacology*; D000595:Amino Acid Sequence; D000818:Animals; D002352:Carrier Proteins / Q000378:metabolism; D017868:Cyclic AMP-Dependent Protein Kinases / Q000378:metabolism; D020558:GTP Phosphohydrolases / Q000037:antagonists & inhibitors / Q000235:genetics / Q000378:metabolism / Q000502:physiology*; D007545:Isoproterenol / Q000494:pharmacology; D050356:Lipid Metabolism / Q000187:drug effects / Q000235:genetics*; D008066:Lipolysis / Q000187:drug effects* / Q000235:genetics; D051379:Mice; D008954:Models, Biological; D000070778:Perilipin-1; D010750:Phosphoproteins / Q000378:metabolism; D034741:RNA, Small Interfering / Q000494:pharmacology; D011943:Receptors, Adrenergic, beta / Q000378:metabolism / Q000502:physiology
chemical_list: D054758:A Kinase Anchor Proteins; D000318:Adrenergic beta-Agonists; D002352:Carrier Proteins; D000070778:Perilipin-1; D010750:Phosphoproteins; D034741:RNA, Small Interfering; D011943:Receptors, Adrenergic, beta; D017868:Cyclic AMP-Dependent Protein Kinases; D020558:GTP Phosphohydrolases; C498809:Opa1 protein, mouse; D007545:Isoproterenol