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PMID: 28377464 Published · ppublish English Journal Article Research Support, Non-U.S. Gov't

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

The EMBO journal ·Vol. 36 ·No. 10 ·2017-00-15 ·Pages 1412-1433

Wilhelm LP, Wendling C, Védie B, Kobayashi T, Chenard MP, Tomasetto C, Drin G, Alpy F

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
MeSH Terms
Biological Transport Carrier Proteins/metabolism Cell Membrane/metabolism Cholesterol/metabolism Endoplasmic Reticulum/metabolism Endosomes/metabolism HeLa Cells Humans Membrane Proteins/metabolism Protein Binding Vesicular Transport Proteins/metabolism
Chemicals
Carrier Proteins Membrane Proteins STARD3 protein, human VAPA protein, human Vesicular Transport Proteins Cholesterol
Authors & Affiliations
8 authors, click to expand affiliations / ORCID
Wilhelm Léa P
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.
Wendling Corinne
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.
Védie Benoît
AP-HP (Assistance Publique - Hôpitaux de Paris), Hôpital Européen Georges Pompidou, Service de Biochimie, Paris, France.
Kobayashi Toshihide
Université de Strasbourg, Illkirch, France. | Laboratory of Biophotonics and Pharmacology, Centre National de la Recherche Scientifique (CNRS), UMR 7213, Illkirch, France.
Chenard Marie-Pierre
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.
Tomasetto Catherine ORCID
Functional Genomics and Cancer Department, Institut de Génétique et de Biologie Moléculaire et Cellulaire (IGBMC), Illkirch, France [email protected] [email protected]. | 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.
Drin Guillaume
Université Côte d'Azur, CNRS Institut de Pharmacologie Moléculaire et Cellulaire, Valbonne, France.
Alpy Fabien ORCID
Functional Genomics and Cancer Department, Institut de Génétique et de Biologie Moléculaire et Cellulaire (IGBMC), Illkirch, France [email protected] [email protected]. | 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.
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Article Info
Journal
The EMBO journal
Abbr.
EMBO J
ISSN
1460-2075
DOI
10.15252/embj.201695917
Email
[email protected]
[email protected]
Published
2017-00-15
Epub
2017-00-04
Pages
1412-1433
Language
English
Region
England
NLM ID
8208664
PMCID
PMC5430228
Subset
IM
External Links
PubMed source DOI: 10.15252/embj.201695917 PMC Full Text View journal details
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