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Changes in the asymmetric distribution of cholesterol in the plasma membrane influence streptolysin O pore formation

ATP-binding cassette A1 (ABCA1) plays a key role in generating high-density lipoprotein (HDL) and preventing atherosclerosis. ABCA1 exports cholesterol and phospholipid to apolipoprotein A-I (apoA-I) in serum to generate HDL. We found that streptolysin O (SLO), a cholesterol-dependent pore-forming t...

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Autores principales: Ogasawara, Fumihiko, Kano, Fumi, Murata, Masayuki, Kimura, Yasuhisa, Kioka, Noriyuki, Ueda, Kazumitsu
Formato: Online Artículo Texto
Lenguaje:English
Publicado: Nature Publishing Group UK 2019
Materias:
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC6418215/
https://www.ncbi.nlm.nih.gov/pubmed/30872611
http://dx.doi.org/10.1038/s41598-019-39973-x
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author Ogasawara, Fumihiko
Kano, Fumi
Murata, Masayuki
Kimura, Yasuhisa
Kioka, Noriyuki
Ueda, Kazumitsu
author_facet Ogasawara, Fumihiko
Kano, Fumi
Murata, Masayuki
Kimura, Yasuhisa
Kioka, Noriyuki
Ueda, Kazumitsu
author_sort Ogasawara, Fumihiko
collection PubMed
description ATP-binding cassette A1 (ABCA1) plays a key role in generating high-density lipoprotein (HDL) and preventing atherosclerosis. ABCA1 exports cholesterol and phospholipid to apolipoprotein A-I (apoA-I) in serum to generate HDL. We found that streptolysin O (SLO), a cholesterol-dependent pore-forming toxin, barely formed pores in ABCA1-expressing cells, even in the absence of apoA-I. Neither cholesterol content in cell membranes nor the amount of SLO bound to cells was affected by ABCA1. On the other hand, binding of the D4 domain of perfringolysin O (PFO) to ABCA1-expressing cells increased, suggesting that the amount of cholesterol in the outer leaflet of the plasma membrane (PM) increased and that the cholesterol dependences of these two toxins differ. Addition of cholesterol to the PM by the MβCD–cholesterol complex dramatically restored SLO pore formation in ABCA1-expressing cells. Therefore, exogenous expression of ABCA1 causes reduction in the cholesterol level in the inner leaflet, thereby suppressing SLO pore formation.
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spelling pubmed-64182152019-03-18 Changes in the asymmetric distribution of cholesterol in the plasma membrane influence streptolysin O pore formation Ogasawara, Fumihiko Kano, Fumi Murata, Masayuki Kimura, Yasuhisa Kioka, Noriyuki Ueda, Kazumitsu Sci Rep Article ATP-binding cassette A1 (ABCA1) plays a key role in generating high-density lipoprotein (HDL) and preventing atherosclerosis. ABCA1 exports cholesterol and phospholipid to apolipoprotein A-I (apoA-I) in serum to generate HDL. We found that streptolysin O (SLO), a cholesterol-dependent pore-forming toxin, barely formed pores in ABCA1-expressing cells, even in the absence of apoA-I. Neither cholesterol content in cell membranes nor the amount of SLO bound to cells was affected by ABCA1. On the other hand, binding of the D4 domain of perfringolysin O (PFO) to ABCA1-expressing cells increased, suggesting that the amount of cholesterol in the outer leaflet of the plasma membrane (PM) increased and that the cholesterol dependences of these two toxins differ. Addition of cholesterol to the PM by the MβCD–cholesterol complex dramatically restored SLO pore formation in ABCA1-expressing cells. Therefore, exogenous expression of ABCA1 causes reduction in the cholesterol level in the inner leaflet, thereby suppressing SLO pore formation. Nature Publishing Group UK 2019-03-14 /pmc/articles/PMC6418215/ /pubmed/30872611 http://dx.doi.org/10.1038/s41598-019-39973-x Text en © The Author(s) 2019 Open Access This article is licensed under a Creative Commons Attribution 4.0 International License, which permits use, sharing, adaptation, distribution and reproduction in any medium or format, as long as you give appropriate credit to the original author(s) and the source, provide a link to the Creative Commons license, and indicate if changes were made. The images or other third party material in this article are included in the article’s Creative Commons license, unless indicated otherwise in a credit line to the material. If material is not included in the article’s Creative Commons license and your intended use is not permitted by statutory regulation or exceeds the permitted use, you will need to obtain permission directly from the copyright holder. To view a copy of this license, visit http://creativecommons.org/licenses/by/4.0/.
spellingShingle Article
Ogasawara, Fumihiko
Kano, Fumi
Murata, Masayuki
Kimura, Yasuhisa
Kioka, Noriyuki
Ueda, Kazumitsu
Changes in the asymmetric distribution of cholesterol in the plasma membrane influence streptolysin O pore formation
title Changes in the asymmetric distribution of cholesterol in the plasma membrane influence streptolysin O pore formation
title_full Changes in the asymmetric distribution of cholesterol in the plasma membrane influence streptolysin O pore formation
title_fullStr Changes in the asymmetric distribution of cholesterol in the plasma membrane influence streptolysin O pore formation
title_full_unstemmed Changes in the asymmetric distribution of cholesterol in the plasma membrane influence streptolysin O pore formation
title_short Changes in the asymmetric distribution of cholesterol in the plasma membrane influence streptolysin O pore formation
title_sort changes in the asymmetric distribution of cholesterol in the plasma membrane influence streptolysin o pore formation
topic Article
url https://www.ncbi.nlm.nih.gov/pmc/articles/PMC6418215/
https://www.ncbi.nlm.nih.gov/pubmed/30872611
http://dx.doi.org/10.1038/s41598-019-39973-x
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