Temporary sequestration of cholesterol and phosphatidylcholine within extracellular domains of ABCA1 during nascent HDL generation

Abstract The quality and quantity of high-density lipoprotein (HDL) in blood plasma are important for preventing coronary artery disease. ATP-binding cassette protein A1 (ABCA1) and apolipoprotein A-I (apoA-I) play essential roles in nascent HDL formation, but controversy persists regarding the mech...

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Autores principales:	Masato Ishigami, Fumihiko Ogasawara, Kohjiro Nagao, Hidehiko Hashimoto, Yasuhisa Kimura, Noriyuki Kioka, Kazumitsu Ueda
Formato:	article
Lenguaje:	EN
Publicado:	Nature Portfolio 2018
Materias:	Medicine R Science Q
Acceso en línea:	https://doaj.org/article/3300c626d1ee4a81ab9c1f0e65515ae8
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spelling	oai:doaj.org-article:3300c626d1ee4a81ab9c1f0e65515ae82021-12-02T15:07:45ZTemporary sequestration of cholesterol and phosphatidylcholine within extracellular domains of ABCA1 during nascent HDL generation10.1038/s41598-018-24428-62045-2322https://doaj.org/article/3300c626d1ee4a81ab9c1f0e65515ae82018-04-01T00:00:00Zhttps://doi.org/10.1038/s41598-018-24428-6https://doaj.org/toc/2045-2322Abstract The quality and quantity of high-density lipoprotein (HDL) in blood plasma are important for preventing coronary artery disease. ATP-binding cassette protein A1 (ABCA1) and apolipoprotein A-I (apoA-I) play essential roles in nascent HDL formation, but controversy persists regarding the mechanism by which nascent HDL is generated. In the “direct loading model”, apoA-I acquires lipids directly from ABCA1 while it is bound to the transporter. By contrast, in the “indirect model”, apoA-I acquires lipids from the specific membrane domains created by ABCA1. In this study, we found that trypsin treatment causes rapid release of phosphatidylcholine (PC) and cholesterol from BHK/ABCA1 cells, and that the time course of lipid release coincides with those of trypsin digestion of extracellular domains (ECDs) of surface ABCA1 and of release of ECD fragments into the medium. This trypsin-dependent lipid release was dependent on ABCA1 ATPase activity, and did not occur in cells that express ABCG1, which exports lipids like ABCA1 but does not have large ECDs. These results suggest that the trypsin-sensitive sites on the cell surface are the large ECDs of ABCA1, and that lipids transported by ABCA1 are temporarily sequestered within the ECDs during nascent HDL formation.Masato IshigamiFumihiko OgasawaraKohjiro NagaoHidehiko HashimotoYasuhisa KimuraNoriyuki KiokaKazumitsu UedaNature PortfolioarticleMedicineRScienceQENScientific Reports, Vol 8, Iss 1, Pp 1-10 (2018)
institution	DOAJ
collection	DOAJ
language	EN
topic	Medicine R Science Q
spellingShingle	Medicine R Science Q Masato Ishigami Fumihiko Ogasawara Kohjiro Nagao Hidehiko Hashimoto Yasuhisa Kimura Noriyuki Kioka Kazumitsu Ueda Temporary sequestration of cholesterol and phosphatidylcholine within extracellular domains of ABCA1 during nascent HDL generation
description	Abstract The quality and quantity of high-density lipoprotein (HDL) in blood plasma are important for preventing coronary artery disease. ATP-binding cassette protein A1 (ABCA1) and apolipoprotein A-I (apoA-I) play essential roles in nascent HDL formation, but controversy persists regarding the mechanism by which nascent HDL is generated. In the “direct loading model”, apoA-I acquires lipids directly from ABCA1 while it is bound to the transporter. By contrast, in the “indirect model”, apoA-I acquires lipids from the specific membrane domains created by ABCA1. In this study, we found that trypsin treatment causes rapid release of phosphatidylcholine (PC) and cholesterol from BHK/ABCA1 cells, and that the time course of lipid release coincides with those of trypsin digestion of extracellular domains (ECDs) of surface ABCA1 and of release of ECD fragments into the medium. This trypsin-dependent lipid release was dependent on ABCA1 ATPase activity, and did not occur in cells that express ABCG1, which exports lipids like ABCA1 but does not have large ECDs. These results suggest that the trypsin-sensitive sites on the cell surface are the large ECDs of ABCA1, and that lipids transported by ABCA1 are temporarily sequestered within the ECDs during nascent HDL formation.
format	article
author	Masato Ishigami Fumihiko Ogasawara Kohjiro Nagao Hidehiko Hashimoto Yasuhisa Kimura Noriyuki Kioka Kazumitsu Ueda
author_facet	Masato Ishigami Fumihiko Ogasawara Kohjiro Nagao Hidehiko Hashimoto Yasuhisa Kimura Noriyuki Kioka Kazumitsu Ueda
author_sort	Masato Ishigami
title	Temporary sequestration of cholesterol and phosphatidylcholine within extracellular domains of ABCA1 during nascent HDL generation
title_short	Temporary sequestration of cholesterol and phosphatidylcholine within extracellular domains of ABCA1 during nascent HDL generation
title_full	Temporary sequestration of cholesterol and phosphatidylcholine within extracellular domains of ABCA1 during nascent HDL generation
title_fullStr	Temporary sequestration of cholesterol and phosphatidylcholine within extracellular domains of ABCA1 during nascent HDL generation
title_full_unstemmed	Temporary sequestration of cholesterol and phosphatidylcholine within extracellular domains of ABCA1 during nascent HDL generation
title_sort	temporary sequestration of cholesterol and phosphatidylcholine within extracellular domains of abca1 during nascent hdl generation
publisher	Nature Portfolio
publishDate	2018
url	https://doaj.org/article/3300c626d1ee4a81ab9c1f0e65515ae8
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Temporary sequestration of cholesterol and phosphatidylcholine within extracellular domains of ABCA1 during nascent HDL generation

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