title: Seipin regulates ER-lipid droplet contacts and cargo delivery.
abstract: Seipin is an endoplasmic reticulum (ER) membrane protein implicated in lipid droplet (LD) biogenesis and mutated in severe congenital lipodystrophy (BSCL2). Here, we show that seipin is stably associated with nascent ER-LD contacts in human cells, typically via one mobile focal point per LD Seipin appears critical for such contacts since ER-LD contacts were completely missing or morphologically aberrant in seipin knockout and BSCL2 patient cells. In parallel, LD mobility was increased and protein delivery from the ER to LDs to promote LD growth was decreased. Moreover, while growing LDs normally acquire lipid and protein constituents from the ER, this process was compromised in seipin-deficient cells. In the absence of seipin, the initial synthesis of neutral lipids from exogenous fatty acid was normal, but fatty acid incorporation into neutral lipids in cells with pre-existing LDs was impaired. Together, our data suggest that seipin helps to connect newly formed LDs to the ER and that by stabilizing ER-LD contacts seipin facilitates the incorporation of protein and lipid cargo into growing LDs in human cells.
authors.affiliation: Department of Anatomy, Faculty of Medicine, University of Helsinki, Helsinki, Finland.|Minerva Foundation Institute for Medical Research, Helsinki, Finland.
authors.forename: Veijo T
authors.initials: VT
authors.lastname: Salo
authors.affiliation: Institute of Biotechnology, University of Helsinki, Helsinki, Finland.
authors.forename: Ilya
authors.initials: I
authors.lastname: Belevich
authors.affiliation: Department of Anatomy, Faculty of Medicine, University of Helsinki, Helsinki, Finland.|Minerva Foundation Institute for Medical Research, Helsinki, Finland.
authors.forename: Shiqian
authors.identifier: 0000-0003-1663-0704
authors.initials: S
authors.lastname: Li
authors.affiliation: Department of Anatomy, Faculty of Medicine, University of Helsinki, Helsinki, Finland.
authors.forename: Leena
authors.initials: L
authors.lastname: Karhinen
authors.affiliation: Institute of Biotechnology, University of Helsinki, Helsinki, Finland.
authors.forename: Helena
authors.initials: H
authors.lastname: Vihinen
authors.affiliation: Sorbonne Universités, UPMC Univ Paris 6, Inserm UMR_S938, Saint-Antoine Research Center, Institute of Cardiometabolism And Nutrition, AP-HP, Saint-Antoine Hospital Department of Molecular Biology and Genetics, Paris, France.
authors.forename: Corinne
authors.initials: C
authors.lastname: Vigouroux
authors.affiliation: l'Institut du Thorax, INSERM CNRS UNIV Nantes, Nantes, France.
authors.forename: Jocelyne
authors.initials: J
authors.lastname: Magré
authors.affiliation: LIMES Institute, Bonn University, Bonn, Germany.
authors.forename: Christoph
authors.initials: C
authors.lastname: Thiele
authors.affiliation: Department of Anatomy, Faculty of Medicine, University of Helsinki, Helsinki, Finland.|Minerva Foundation Institute for Medical Research, Helsinki, Finland.
authors.forename: Maarit
authors.initials: M
authors.lastname: Hölttä-Vuori
authors.affiliation: Institute of Biotechnology, University of Helsinki, Helsinki, Finland.
authors.forename: Eija
authors.initials: E
authors.lastname: Jokitalo
authors.affiliation: Department of Anatomy, Faculty of Medicine, University of Helsinki, Helsinki, Finland elina.ikonen@helsinki.fi.|Minerva Foundation Institute for Medical Research, Helsinki, Finland.
authors.forename: Elina
authors.initials: E
authors.lastname: Ikonen
mesh_terms: D002478:Cells, Cultured; D004721:Endoplasmic Reticulum / Q000378:metabolism*; D044388:GTP-Binding Protein gamma Subunits / Q000235:genetics / Q000378:metabolism*; D055786:Gene Knockout Techniques; D006801:Humans; D066292:Lipid Droplets / Q000378:metabolism*; D008954:Models, Biological
chemical_list: C432679:BSCL2 protein, human; D044388:GTP-Binding Protein gamma Subunits
keywords: electron microscopy; lipid storage; lipodystrophy; membrane contact sites