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

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.

Source: EMBO Journal - May 15, 2017 Category: Molecular Biology Authors: Wilhelm, L. P., Wendling, C., Vedie, B., Kobayashi, T., Chenard, M.-P., Tomasetto, C., Drin, G., Alpy, F. Tags: Membrane & Intracellular Transport Articles Source Type: research