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

Autor:	Fumihiko Ogasawara, Yasuhisa Kimura, Kazumitsu Ueda, Noriyuki Kioka, Masato Ishigami, Kohjiro Nagao, Hidehiko Hashimoto
Jazyk:	angličtina
Rok vydání:	2018
Předmět:	0301 basic medicine Apolipoprotein B genetic structures Science Plasma protein binding Models Biological Article 03 medical and health sciences chemistry.chemical_compound Phosphatidylcholine Extracellular polycyclic compounds Animals Humans Protein Interaction Domains and Motifs Cell Line Transformed Multidisciplinary 030102 biochemistry & molecular biology biology Cholesterol Cell Membrane nutritional and metabolic diseases Biological Transport Lipid metabolism hemic and immune systems Lipid Metabolism Cell biology 030104 developmental biology chemistry ABCA1 Phosphatidylcholines biology.protein Medicine ATP-Binding Cassette Transporters lipids (amino acids peptides and proteins) Lipoproteins HDL ATP Binding Cassette Transporter 1 Protein Binding Lipoprotein
Zdroj:	Scientific Reports, Vol 8, Iss 1, Pp 1-10 (2018) Scientific Reports
ISSN:	2045-2322
Popis:	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.
Databáze:	OpenAIRE
Externí odkaz:	https://explore.openaire.eu/search/publication?articleId=doi_dedup___::7a2fb17b3b4f072589d4daa071e9d68e https://doaj.org/article/3300c626d1ee4a81ab9c1f0e65515ae8 Zobrazit plný text záznamu Plný text ve formátu PDF Plný text ve formátu HTML
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