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ABCA1 and cholesterol transfer protein Aster-A promote an asymmetric cholesterol distribution in the plasma membrane
Cholesterol is a major and essential component of the mammalian cell plasma membrane (PM), and the loss of cholesterol homeostasis leads to various pathologies. Cellular cholesterol uptake and synthesis are regulated by a cholesterol sensor in the endoplasmic reticulum (ER). However, it remains uncl...
Autores principales: | , |
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Formato: | Online Artículo Texto |
Lenguaje: | English |
Publicado: |
American Society for Biochemistry and Molecular Biology
2022
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Materias: | |
Acceso en línea: | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC9747601/ https://www.ncbi.nlm.nih.gov/pubmed/36395885 http://dx.doi.org/10.1016/j.jbc.2022.102702 |
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author | Ogasawara, Fumihiko Ueda, Kazumitsu |
author_facet | Ogasawara, Fumihiko Ueda, Kazumitsu |
author_sort | Ogasawara, Fumihiko |
collection | PubMed |
description | Cholesterol is a major and essential component of the mammalian cell plasma membrane (PM), and the loss of cholesterol homeostasis leads to various pathologies. Cellular cholesterol uptake and synthesis are regulated by a cholesterol sensor in the endoplasmic reticulum (ER). However, it remains unclear how changes in the cholesterol level of the PM are recognized. Here, we show that the sensing of cholesterol in the PM depends on ABCA1 and the cholesterol transfer protein Aster-A, which cooperatively maintain the asymmetric transbilayer cholesterol distribution in the PM. We demonstrate that ABCA1 translocates (flops) cholesterol from the inner leaflet of the PM to the outer leaflet of the PM to maintain a low inner leaflet cholesterol level. We also found that when inner cholesterol levels were increased, Aster-A was recruited to the PM–ER contact site to transfer cholesterol to the ER. These results suggest that ABCA1 could promote an asymmetric cholesterol distribution to suppress Aster-A recruitment to the PM–ER contact site to maintain intracellular cholesterol homeostasis. |
format | Online Article Text |
id | pubmed-9747601 |
institution | National Center for Biotechnology Information |
language | English |
publishDate | 2022 |
publisher | American Society for Biochemistry and Molecular Biology |
record_format | MEDLINE/PubMed |
spelling | pubmed-97476012022-12-15 ABCA1 and cholesterol transfer protein Aster-A promote an asymmetric cholesterol distribution in the plasma membrane Ogasawara, Fumihiko Ueda, Kazumitsu J Biol Chem Research Article Cholesterol is a major and essential component of the mammalian cell plasma membrane (PM), and the loss of cholesterol homeostasis leads to various pathologies. Cellular cholesterol uptake and synthesis are regulated by a cholesterol sensor in the endoplasmic reticulum (ER). However, it remains unclear how changes in the cholesterol level of the PM are recognized. Here, we show that the sensing of cholesterol in the PM depends on ABCA1 and the cholesterol transfer protein Aster-A, which cooperatively maintain the asymmetric transbilayer cholesterol distribution in the PM. We demonstrate that ABCA1 translocates (flops) cholesterol from the inner leaflet of the PM to the outer leaflet of the PM to maintain a low inner leaflet cholesterol level. We also found that when inner cholesterol levels were increased, Aster-A was recruited to the PM–ER contact site to transfer cholesterol to the ER. These results suggest that ABCA1 could promote an asymmetric cholesterol distribution to suppress Aster-A recruitment to the PM–ER contact site to maintain intracellular cholesterol homeostasis. American Society for Biochemistry and Molecular Biology 2022-11-14 /pmc/articles/PMC9747601/ /pubmed/36395885 http://dx.doi.org/10.1016/j.jbc.2022.102702 Text en © 2022 The Authors https://creativecommons.org/licenses/by/4.0/This is an open access article under the CC BY license (http://creativecommons.org/licenses/by/4.0/). |
spellingShingle | Research Article Ogasawara, Fumihiko Ueda, Kazumitsu ABCA1 and cholesterol transfer protein Aster-A promote an asymmetric cholesterol distribution in the plasma membrane |
title | ABCA1 and cholesterol transfer protein Aster-A promote an asymmetric cholesterol distribution in the plasma membrane |
title_full | ABCA1 and cholesterol transfer protein Aster-A promote an asymmetric cholesterol distribution in the plasma membrane |
title_fullStr | ABCA1 and cholesterol transfer protein Aster-A promote an asymmetric cholesterol distribution in the plasma membrane |
title_full_unstemmed | ABCA1 and cholesterol transfer protein Aster-A promote an asymmetric cholesterol distribution in the plasma membrane |
title_short | ABCA1 and cholesterol transfer protein Aster-A promote an asymmetric cholesterol distribution in the plasma membrane |
title_sort | abca1 and cholesterol transfer protein aster-a promote an asymmetric cholesterol distribution in the plasma membrane |
topic | Research Article |
url | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC9747601/ https://www.ncbi.nlm.nih.gov/pubmed/36395885 http://dx.doi.org/10.1016/j.jbc.2022.102702 |
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