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


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.

SUBMITTER: Wilhelm LP 

PROVIDER: S-EPMC5430228 | biostudies-literature | 2017 May

REPOSITORIES: biostudies-literature

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

Wilhelm Léa P LP   Wendling Corinne C   Védie Benoît B   Kobayashi Toshihide T   Chenard Marie-Pierre MP   Tomasetto Catherine C   Drin Guillaume G   Alpy Fabien F  

The EMBO journal 20170404 10


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 <i>in situ</i> cholesterol labeling and quantification, we demonstrated that STARD3 induces cholesterol accumulation in endosomes at the expense of the plasma membrane. STARD3-mediated cholesterol  ...[more]

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