Abstract:
:ABCA1 exports cholesterol and phospholipids from cells by a multistep pathway that involves forming cell surface lipid domains, solubilizing these lipids by apolipoproteins, binding of apolipoproteins to ABCA1, and activating signaling processes. Here we used a mutational analysis approach to evaluate the relationship between these events. We prepared seven naturally occurring mutants and one artificial missense mutant of ABCA1 with varying degrees of impaired function, expressed them to similar levels as wild-type ABCA1 on the cell surface of BHK cells, and measured ABCA1-dependent lipid export, apolipoprotein A-I (apoA-I) binding, and signaling activities. Linear regression analyses showed that cholesterol and phospholipid efflux and cellular apoA-I binding correlated significantly with the ability of ABCA1 to form cell surface lipid domains. Lipid export and cellular apoA-I binding activities and formation of lipid domains also correlated with the amount of apoA-I that could be cross-linked to ABCA1. Moreover, each of these lipid export and apoA-I binding activities correlated with apoA-I-induced Janus kinase 2 (JAK2) activation. Thus, these missense mutations in ABCA1 impair lipid export, apoA-I binding, and apoA-I-stimulated JAK2 activities to similar extents, indicating that these processes are highly interactive components of a pathway that functions to export lipids from cells.
journal_name
J Lipid Resjournal_title
Journal of lipid researchauthors
Vaughan AM,Tang C,Oram JFdoi
10.1194/jlr.M800366-JLR200subject
Has Abstractpub_date
2009-02-01 00:00:00pages
285-92issue
2eissn
0022-2275issn
1539-7262pii
M800366-JLR200journal_volume
50pub_type
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journal_title:Journal of lipid research
pub_type: 杂志文章
doi:10.1194/jlr.D008391
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journal_title:Journal of lipid research
pub_type: 杂志文章
doi:
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journal_title:Journal of lipid research
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journal_title:Journal of lipid research
pub_type: 杂志文章
doi:
更新日期:1998-03-01 00:00:00
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journal_title:Journal of lipid research
pub_type: 杂志文章
doi:10.1194/jlr.P080143
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journal_title:Journal of lipid research
pub_type: 杂志文章
doi:
更新日期:1978-02-01 00:00:00
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journal_title:Journal of lipid research
pub_type: 杂志文章
doi:10.1194/jlr.P085050
更新日期:2018-06-01 00:00:00
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journal_title:Journal of lipid research
pub_type: 杂志文章
doi:10.1194/jlr.M013292
更新日期:2011-04-01 00:00:00
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journal_title:Journal of lipid research
pub_type: 杂志文章
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更新日期:2015-07-01 00:00:00
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journal_title:Journal of lipid research
pub_type: 杂志文章
doi:
更新日期:1967-05-01 00:00:00
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journal_title:Journal of lipid research
pub_type: 杂志文章
doi:
更新日期:1994-11-01 00:00:00
abstract::The skin surface represents our interface with the external environment, and as such, is our first line of defense against microbial colonization and infection. Lipids at the skin surface are thought to underlie at least part of an antimicrobial barrier. Some of these lipids are synthesized in the epidermis and are ca...
journal_title:Journal of lipid research
pub_type: 杂志文章,评审
doi:10.1194/jlr.R700016-JLR200
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journal_title:Journal of lipid research
pub_type: 杂志文章
doi:10.1194/jlr.M027102
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journal_title:Journal of lipid research
pub_type: 杂志文章
doi:10.1194/jlr.M300016-JLR200
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journal_title:Journal of lipid research
pub_type: 杂志文章
doi:
更新日期:1974-09-01 00:00:00
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journal_title:Journal of lipid research
pub_type: 杂志文章
doi:
更新日期:1998-05-01 00:00:00
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journal_title:Journal of lipid research
pub_type: 杂志文章
doi:10.1194/jlr.M800626
更新日期:2010-05-01 00:00:00
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journal_title:Journal of lipid research
pub_type: 杂志文章
doi:
更新日期:1976-11-01 00:00:00
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journal_title:Journal of lipid research
pub_type: 杂志文章
doi:
更新日期:1996-06-01 00:00:00
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journal_title:Journal of lipid research
pub_type: 杂志文章
doi:
更新日期:2000-02-01 00:00:00
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journal_title:Journal of lipid research
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doi:
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journal_title:Journal of lipid research
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doi:
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journal_title:Journal of lipid research
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journal_title:Journal of lipid research
pub_type: 杂志文章
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journal_title:Journal of lipid research
pub_type: 临床试验,杂志文章,随机对照试验
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journal_title:Journal of lipid research
pub_type: 杂志文章
doi:10.1194/jlr.M600136-JLR200
更新日期:2006-11-01 00:00:00
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journal_title:Journal of lipid research
pub_type: 杂志文章
doi:10.1194/jlr.M400391-JLR200
更新日期:2005-03-01 00:00:00
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pub_type: 杂志文章
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更新日期:2010-08-01 00:00:00
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journal_title:Journal of lipid research
pub_type: 杂志文章
doi:
更新日期:1993-09-01 00:00:00
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journal_title:Journal of lipid research
pub_type: 杂志文章
doi:
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