2. Academic Validation
  3. STARD3 mediates endoplasmic reticulum-to-endosome cholesterol transport at membrane contact sites

STARD3 mediates endoplasmic reticulum-to-endosome cholesterol transport at membrane contact sites

  • EMBO J. 2017 May 15;36(10):1412-1433. doi: 10.15252/embj.201695917.
Léa P Wilhelm 1 2 3 4,  Corinne Wendling 1 2 3 4,  Benoît Védie 5,  Toshihide Kobayashi 4 6,  Marie-Pierre Chenard 1 4 7,  Catherine Tomasetto 8 2 3 4,  Guillaume Drin 9,  Fabien Alpy 8 2 3 4
Affiliations

Affiliations

  • 1 Functional Genomics and Cancer Department, Institut de Génétique et de Biologie Moléculaire et Cellulaire (IGBMC), Illkirch, France.
  • 2 Institut National de la Santé et de la Recherche Médicale (INSERM), U 964, Illkirch, France.
  • 3 Centre National de la Recherche Scientifique (CNRS), UMR 7104, Illkirch, France.
  • 4 Université de Strasbourg, Illkirch, France.
  • 5 AP-HP (Assistance Publique - Hôpitaux de Paris), Hôpital Européen Georges Pompidou, Service de Biochimie, Paris, France.
  • 6 Laboratory of Biophotonics and Pharmacology, Centre National de la Recherche Scientifique (CNRS), UMR 7213, Illkirch, France.
  • 7 Service d'Anatomie Pathologique Générale, Centre Hospitalier Universitaire de Hautepierre, Strasbourg, France.
  • 8 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.
  • 9 Université Côte d'Azur, CNRS Institut de Pharmacologie Moléculaire et Cellulaire, Valbonne, France.
PMID: 28377464 DOI: 10.15252/embj.201695917
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 using in situ Cholesterol 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 vitro reconstitution 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.

Keywords

cholesterol; endoplasmic reticulum; endosome; lipid transfer protein; membrane contact site.

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