Cargando…
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 us...
Autores principales: | , , , , , , , |
---|---|
Formato: | Online Artículo Texto |
Lenguaje: | English |
Publicado: |
John Wiley and Sons Inc.
2017
|
Materias: | |
Acceso en línea: | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC5430228/ https://www.ncbi.nlm.nih.gov/pubmed/28377464 http://dx.doi.org/10.15252/embj.201695917 |
_version_ | 1783236175989833728 |
---|---|
author | Wilhelm, Léa P Wendling, Corinne Védie, Benoît Kobayashi, Toshihide Chenard, Marie‐Pierre Tomasetto, Catherine Drin, Guillaume Alpy, Fabien |
author_facet | Wilhelm, Léa P Wendling, Corinne Védie, Benoît Kobayashi, Toshihide Chenard, Marie‐Pierre Tomasetto, Catherine Drin, Guillaume Alpy, Fabien |
author_sort | Wilhelm, Léa P |
collection | PubMed |
description | 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. |
format | Online Article Text |
id | pubmed-5430228 |
institution | National Center for Biotechnology Information |
language | English |
publishDate | 2017 |
publisher | John Wiley and Sons Inc. |
record_format | MEDLINE/PubMed |
spelling | pubmed-54302282017-05-17 STARD3 mediates endoplasmic reticulum‐to‐endosome cholesterol transport at membrane contact sites Wilhelm, Léa P Wendling, Corinne Védie, Benoît Kobayashi, Toshihide Chenard, Marie‐Pierre Tomasetto, Catherine Drin, Guillaume Alpy, Fabien EMBO J Articles 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. John Wiley and Sons Inc. 2017-04-04 2017-05-15 /pmc/articles/PMC5430228/ /pubmed/28377464 http://dx.doi.org/10.15252/embj.201695917 Text en © 2017 The Authors. Published under the terms of the CC BY NC ND 4.0 license This is an open access article under the terms of the Creative Commons Attribution‐NonCommercial‐NoDerivs 4.0 (http://creativecommons.org/licenses/by-nc-nd/4.0/) License, which permits use and distribution in any medium, provided the original work is properly cited, the use is non‐commercial and no modifications or adaptations are made. |
spellingShingle | Articles Wilhelm, Léa P Wendling, Corinne Védie, Benoît Kobayashi, Toshihide Chenard, Marie‐Pierre Tomasetto, Catherine Drin, Guillaume Alpy, Fabien STARD3 mediates endoplasmic reticulum‐to‐endosome cholesterol transport at membrane contact sites |
title |
STARD3 mediates endoplasmic reticulum‐to‐endosome cholesterol transport at membrane contact sites |
title_full |
STARD3 mediates endoplasmic reticulum‐to‐endosome cholesterol transport at membrane contact sites |
title_fullStr |
STARD3 mediates endoplasmic reticulum‐to‐endosome cholesterol transport at membrane contact sites |
title_full_unstemmed |
STARD3 mediates endoplasmic reticulum‐to‐endosome cholesterol transport at membrane contact sites |
title_short |
STARD3 mediates endoplasmic reticulum‐to‐endosome cholesterol transport at membrane contact sites |
title_sort | stard3 mediates endoplasmic reticulum‐to‐endosome cholesterol transport at membrane contact sites |
topic | Articles |
url | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC5430228/ https://www.ncbi.nlm.nih.gov/pubmed/28377464 http://dx.doi.org/10.15252/embj.201695917 |
work_keys_str_mv | AT wilhelmleap stard3mediatesendoplasmicreticulumtoendosomecholesteroltransportatmembranecontactsites AT wendlingcorinne stard3mediatesendoplasmicreticulumtoendosomecholesteroltransportatmembranecontactsites AT vediebenoit stard3mediatesendoplasmicreticulumtoendosomecholesteroltransportatmembranecontactsites AT kobayashitoshihide stard3mediatesendoplasmicreticulumtoendosomecholesteroltransportatmembranecontactsites AT chenardmariepierre stard3mediatesendoplasmicreticulumtoendosomecholesteroltransportatmembranecontactsites AT tomasettocatherine stard3mediatesendoplasmicreticulumtoendosomecholesteroltransportatmembranecontactsites AT dringuillaume stard3mediatesendoplasmicreticulumtoendosomecholesteroltransportatmembranecontactsites AT alpyfabien stard3mediatesendoplasmicreticulumtoendosomecholesteroltransportatmembranecontactsites |