文章基本信息

标题：Distinct sites on ABCA1 control distinct steps required for cellular release of phospholipids
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作者：Véronique Rigot ; Yannick Hamon ; Olivier Chambenoit 等
期刊名称：JLR Papers In Press
印刷版ISSN：0022-2275
电子版ISSN：1539-7262
出版年度：2002
卷号：43
期号：12
页码：2077-2086
DOI：10.1194/jlr.M200279-JLR200
语种：English
出版社：American Society for Biochemistry and Molecular Biology
摘要：The loss of ABCA1 function leads to Tangier dyslipidemia in humans and to a Tangier-like phenotype in mice, by impairing the transformation of nascent apolipoproteins into mature HDL particles. Mechanistically this ensues from the inability of cells to release membrane lipids and cholesterol. Whereas the ability of ABCA1 to promote phospholipid effluxes, surface binding of apolipoproteins and outward flip of membrane lipids has been documented, the relationship between this series of ABCA1-dependent events is still elusive. Here we provide evidence that i ) lipid effluxes require both flip of membrane lipids and binding of apolipoproteins to the cell surface, ii ) apolipoprotein A-I binding depends on structural determinants on ABCA1, and iii ) phospholipid effluxes can be modulated by engineered mutations on the structural determinants identified on ABCA1.