Functional Genomics and Cancer Department, Institute of Genetics and Molecular and Cellular Biology (IGBMC), Illkirch, France. STARD3 mediates endoplasmic reticulum-toendosome cholesterol transport at membrane contact sites
EMBO J. 2017 May 15;36(10):1412-1433. doi: 10.15252/embj.201695917. Wilhelm LP, Wendling C, Védie B, Kobayashi T, Chenard MP, Tomasetto C, Drin G, Alpy F.
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Lea WILHELM, 27 years old, obtained a Bachelor's degree in Life Science and a Master's Degree in Cellular and Molecular Physiopathology at the University of Strasbourg. She recently completed her thesis in the laboratory of Dr. Catherine TOMASETTO at the Institute of Genetics and Molecular and Cellular Biology (IGBMC). Her work published in the EMBO journal reveals the involvement of the STARD3 protein in the distribution of cellular cholesterol. By forming membrane contacts between two cellular organelles, STARD3 makes it possible to transport cholesterol from one organelle to the other along an unexplored pathway.
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PhD Student, Tomasetto Team
Institute of Genetics and Molecular and Cellular Biology
Functional Genomics and Cancer Department
Team Catherine Tomasetto
67404 ILLKIRCH
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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.