title: STARD3 mediates endoplasmic reticulum-to-endosome cholesterol transport at membrane contact sites.
abstract: StAR-related lipid transfer domain-3 (STARD3) is a sterol-binding protein that creates endoplasmic reticulum (ER)-endosome contact sites. How this protein, at the crossroad between sterol uptake and synthesis pathways, impacts the intracellular distribution of this lipid was ill-defined. Here, by usingin situcholesterol labeling and quantification, we demonstrated that STARD3 induces cholesterol accumulation in endosomes at the expense of the plasma membrane. STARD3-mediated cholesterol routing depends both on its lipid transfer activity and its ability to create ER-endosome contacts. Corroborating this,in vitroreconstitution assays indicated that STARD3 and its ER-anchored partner, Vesicle-associated membrane protein-associated protein (VAP), assemble into a machine that allows a highly efficient transport of cholesterol within membrane contacts. Thus, STARD3 is a cholesterol transporter scaffolding ER-endosome contacts and modulating cellular cholesterol repartition by delivering cholesterol to endosomes.
authors.affiliation: Functional Genomics and Cancer Department, Institut de Génétique et de Biologie Moléculaire et Cellulaire (IGBMC), Illkirch, France.|Institut National de la Santé et de la Recherche Médicale (INSERM), U 964, Illkirch, France.|Centre National de la Recherche Scientifique (CNRS), UMR 7104, Illkirch, France.|Université de Strasbourg, Illkirch, France.
authors.forename: Léa P
authors.initials: LP
authors.lastname: Wilhelm
authors.affiliation: Functional Genomics and Cancer Department, Institut de Génétique et de Biologie Moléculaire et Cellulaire (IGBMC), Illkirch, France.|Institut National de la Santé et de la Recherche Médicale (INSERM), U 964, Illkirch, France.|Centre National de la Recherche Scientifique (CNRS), UMR 7104, Illkirch, France.|Université de Strasbourg, Illkirch, France.
authors.forename: Corinne
authors.initials: C
authors.lastname: Wendling
authors.affiliation: AP-HP (Assistance Publique - Hôpitaux de Paris), Hôpital Européen Georges Pompidou, Service de Biochimie, Paris, France.
authors.forename: Benoît
authors.initials: B
authors.lastname: Védie
authors.affiliation: Université de Strasbourg, Illkirch, France.|Laboratory of Biophotonics and Pharmacology, Centre National de la Recherche Scientifique (CNRS), UMR 7213, Illkirch, France.
authors.forename: Toshihide
authors.initials: T
authors.lastname: Kobayashi
authors.affiliation: Functional Genomics and Cancer Department, Institut de Génétique et de Biologie Moléculaire et Cellulaire (IGBMC), Illkirch, France.|Université de Strasbourg, Illkirch, France.|Service d'Anatomie Pathologique Générale, Centre Hospitalier Universitaire de Hautepierre, Strasbourg, France.
authors.forename: Marie-Pierre
authors.initials: MP
authors.lastname: Chenard
authors.affiliation: Functional Genomics and Cancer Department, Institut de Génétique et de Biologie Moléculaire et Cellulaire (IGBMC), Illkirch, France catherine-laure.tomasetto@igbmc.fr fabien.alpy@igbmc.fr.|Institut National de la Santé et de la Recherche Médicale (INSERM), U 964, Illkirch, France.|Centre National de la Recherche Scientifique (CNRS), UMR 7104, Illkirch, France.|Université de Strasbourg, Illkirch, France.
authors.forename: Catherine
authors.identifier: 0000-0002-1811-5848
authors.initials: C
authors.lastname: Tomasetto
authors.affiliation: Université Côte d'Azur, CNRS Institut de Pharmacologie Moléculaire et Cellulaire, Valbonne, France.
authors.forename: Guillaume
authors.initials: G
authors.lastname: Drin
authors.affiliation: Functional Genomics and Cancer Department, Institut de Génétique et de Biologie Moléculaire et Cellulaire (IGBMC), Illkirch, France catherine-laure.tomasetto@igbmc.fr fabien.alpy@igbmc.fr.|Institut National de la Santé et de la Recherche Médicale (INSERM), U 964, Illkirch, France.|Centre National de la Recherche Scientifique (CNRS), UMR 7104, Illkirch, France.|Université de Strasbourg, Illkirch, France.
authors.forename: Fabien
authors.identifier: 0000-0002-0526-0720
authors.initials: F
authors.lastname: Alpy
mesh_terms: D001692:Biological Transport; D002352:Carrier Proteins / Q000378:metabolism*; D002462:Cell Membrane / Q000378:metabolism*; D002784:Cholesterol / Q000378:metabolism*; D004721:Endoplasmic Reticulum / Q000378:metabolism*; D011992:Endosomes / Q000378:metabolism*; D006367:HeLa Cells; D006801:Humans; D008565:Membrane Proteins / Q000378:metabolism*; D011485:Protein Binding; D033921:Vesicular Transport Proteins / Q000378:metabolism
chemical_list: D002352:Carrier Proteins; D008565:Membrane Proteins; C105684:STARD3 protein, human; C114051:VAPA protein, human; D033921:Vesicular Transport Proteins; D002784:Cholesterol
keywords: cholesterol; endoplasmic reticulum; endosome; lipid transfer protein; membrane contact site