title: Spatial control of lipid droplet proteins by the ERAD ubiquitin ligase Doa10.
abstract: The endoplasmic reticulum (ER) plays a central role in the biogenesis of most membrane proteins. Among these are proteins localized to the surface of lipid droplets (LDs), fat storage organelles delimited by a phospholipid monolayer. The LD monolayer is often continuous with the membrane of the ER allowing certain membrane proteins to diffuse between the two organelles. In these connected organelles, how some proteins concentrate specifically at the surface of LDs is not known. Here, we show that the ERAD ubiquitin ligase Doa10 controls the levels of some LD proteins. Their degradation is dependent on the localization to the ER and appears independent of the folding state. Moreover, we show that by degrading the ER pool of these LD proteins, ERAD contributes to restrict their localization to LDs. The signals for LD targeting and Doa10-mediated degradation overlap, indicating that these are competing events. This spatial control of protein localization is a novel function of ERAD that might contribute to generate functional diversity in a continuous membrane system.
authors.affiliation: Centre for Genomic Regulation (CRG), Barcelona Institute of Science and Technology, Barcelona, Spain Universitat Pompeu Fabra (UPF), Barcelona, Spain.
authors.forename: Annamaria
authors.initials: A
authors.lastname: Ruggiano
authors.affiliation: Centre for Genomic Regulation (CRG), Barcelona Institute of Science and Technology, Barcelona, Spain Universitat Pompeu Fabra (UPF), Barcelona, Spain.
authors.forename: Gabriel
authors.initials: G
authors.lastname: Mora
authors.affiliation: Centre for Genomic Regulation (CRG), Barcelona Institute of Science and Technology, Barcelona, Spain Universitat Pompeu Fabra (UPF), Barcelona, Spain.
authors.forename: Laura
authors.initials: L
authors.lastname: Buxó
authors.affiliation: Centre for Genomic Regulation (CRG), Barcelona Institute of Science and Technology, Barcelona, Spain Universitat Pompeu Fabra (UPF), Barcelona, Spain pedro.carvalho@crg.eu.
authors.forename: Pedro
authors.identifier: 0000-0002-9691-5277
authors.initials: P
authors.lastname: Carvalho
mesh_terms: D015966:Gene Expression Regulation, Fungal; D000070136:Lipid Droplet Associated Proteins / Q000378:metabolism*; D059748:Proteolysis; D029701:Saccharomyces cerevisiae Proteins / Q000378:metabolism*; D044767:Ubiquitin-Protein Ligases / Q000378:metabolism*
chemical_list: D000070136:Lipid Droplet Associated Proteins; D029701:Saccharomyces cerevisiae Proteins; C091362:SSM4 protein, S cerevisiae; D044767:Ubiquitin-Protein Ligases
keywords: Doa10; ERAD; endoplasmic reticulum; lipid droplets; protein degradation