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Apolipoprotein A‐1 interaction with plasma membrane lipid rafts controls cholesterol export from macrophages
Author(s) -
Gaus Katharina,
Kritharides Leonard,
Schmitz Gerd,
Boettcher Alfred,
Drobnik Wolfgang,
Langmann Thomas,
Quinn Carmel M.,
Death Alison,
Dean Roger T.,
Jessup Wendy
Publication year - 2004
Publication title -
the faseb journal
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.709
H-Index - 277
eISSN - 1530-6860
pISSN - 0892-6638
DOI - 10.1096/fj.03-0486fje
Subject(s) - efflux , cholesterol , lipid raft , raft , chemistry , apolipoprotein b , membrane , reverse cholesterol transport , biochemistry , lipoprotein , organic chemistry , copolymer , polymer
Cholesterol efflux to apolipoprotein A‐1 (apoA‐1) from cholesterol‐loaded macrophages is an important anti‐atherosclerotic mechanism in reverse cholesterol transport. We recently provided kinetic evidence for two distinct pathways for cholesterol efflux to apoA‐1 [Gaus et al. (2001) Biochemistry 40, 9363]. Cholesterol efflux from two membrane pools occurs sequentially with different kinetics; a small pool rapidly effluxed over the first hour, followed by progressive release from a major, slow efflux pool over several hours. In the present study, we propose that the rapid and slow cholesterol efflux pools represent cholesterol derived from lipid raft and nonraft domains of the plasma membrane, respectively. We provide direct evidence that apoA‐1 binds to both lipid raft and nonraft domains of the macrophage plasma membrane. Conditions that selectively deplete plasma membrane lipid raft cholesterol, such as incorporation of 7‐ketocholesterol or rapid exposure to cyclodextrins, block apoA‐1 binding to these domains but also inhibit cholesterol efflux from the major, slow pool. We propose that cholesterol exported to apoA‐1 from this major slow efflux pool derives from nonraft regions of the plasma membrane but that the interaction of apoA‐1 with lipid rafts is necessary to stimulate this efflux.