Apolipoprotein A-1 interaction with plasma membrane lipid rafts controls cholesterol export from macrophages

Katharina Gaus, L Kritharides, Gerd Schmitz, Alfred Boettcher, Wolfgang Drobnik, Thomas Langmann, Carmel Quinn, Alison Death, Roger Dean, W Jessup

Research output: Contribution to journalArticle

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Abstract

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.
Original languageEnglish
Pages (from-to)574-576
Number of pages3
JournalThe FASEB Journal
Volume18
Issue number3
DOIs
Publication statusPublished - 2004

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Macrophages
Apolipoprotein A-I
Cell membranes
Membrane Lipids
Cholesterol
Cell Membrane
Lipids
Biochemistry
Kinetics
Cyclodextrins
Membranes

Cite this

Gaus, K., Kritharides, L., Schmitz, G., Boettcher, A., Drobnik, W., Langmann, T., ... Jessup, W. (2004). Apolipoprotein A-1 interaction with plasma membrane lipid rafts controls cholesterol export from macrophages. The FASEB Journal, 18(3), 574-576. https://doi.org/10.1096/fj.03-0486fje
Gaus, Katharina ; Kritharides, L ; Schmitz, Gerd ; Boettcher, Alfred ; Drobnik, Wolfgang ; Langmann, Thomas ; Quinn, Carmel ; Death, Alison ; Dean, Roger ; Jessup, W. / Apolipoprotein A-1 interaction with plasma membrane lipid rafts controls cholesterol export from macrophages. In: The FASEB Journal. 2004 ; Vol. 18, No. 3. pp. 574-576.
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abstract = "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.",
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Gaus, K, Kritharides, L, Schmitz, G, Boettcher, A, Drobnik, W, Langmann, T, Quinn, C, Death, A, Dean, R & Jessup, W 2004, 'Apolipoprotein A-1 interaction with plasma membrane lipid rafts controls cholesterol export from macrophages', The FASEB Journal, vol. 18, no. 3, pp. 574-576. https://doi.org/10.1096/fj.03-0486fje

Apolipoprotein A-1 interaction with plasma membrane lipid rafts controls cholesterol export from macrophages. / Gaus, Katharina; Kritharides, L; Schmitz, Gerd; Boettcher, Alfred; Drobnik, Wolfgang; Langmann, Thomas; Quinn, Carmel; Death, Alison; Dean, Roger; Jessup, W.

In: The FASEB Journal, Vol. 18, No. 3, 2004, p. 574-576.

Research output: Contribution to journalArticle

TY - JOUR

T1 - Apolipoprotein A-1 interaction with plasma membrane lipid rafts controls cholesterol export from macrophages

AU - Gaus, Katharina

AU - Kritharides, L

AU - Schmitz, Gerd

AU - Boettcher, Alfred

AU - Drobnik, Wolfgang

AU - Langmann, Thomas

AU - Quinn, Carmel

AU - Death, Alison

AU - Dean, Roger

AU - Jessup, W

PY - 2004

Y1 - 2004

N2 - 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.

AB - 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.

U2 - 10.1096/fj.03-0486fje

DO - 10.1096/fj.03-0486fje

M3 - Article

VL - 18

SP - 574

EP - 576

JO - FASEB Journal

JF - FASEB Journal

SN - 0892-6638

IS - 3

ER -