STARD3 mediates endoplasmic reticulum-to-endosome cholesterol transport at membrane contact sites.
Fiche publication
Date publication
avril 2017
Journal
The EMBO journal
Auteurs
Membres identifiés du Cancéropôle Est :
Dr ALPY Fabien, Pr CHENARD Marie-Pierre, Dr TOMASETTO Catherine, Dr KOBAYASHI Toshihide
Tous les auteurs :
Wilhelm LP, Wendling C, Védie B, Kobayashi T, Chenard MP, Tomasetto C, Drin G, Alpy F
Lien Pubmed
Résumé
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.
Mots clés
cholesterol, endoplasmic reticulum, endosome, lipid transfer protein, membrane contact site
Référence
EMBO J.. 2017 Apr;: