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

https://www.ncbi.nlm.nih.gov/pubmed/28377464

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.