Molecular interactions between apoE and ABCA1

Krimbou, Larbi; Denis, Maxime; Haidar, Bassam; Carrier, Marilyn; Marcil, Michel; Genest, Jacques

doi:10.1194/jlr.m300418-jlr200

Cited by 115 publications

(90 citation statements)

References 56 publications

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“…Indeed, previous studies have documented that apoA-I deletion mutants lacking residues 187-243 of the C-terminal domain (⌬(187-243)) exhibit both reduced cell surface binding and the ability to promote lipid efflux (9,11,15). Furthermore, we and others have previously shown that lipid association with apoA-I or apoE3 reduced their ability to interact with ABCA1 (20,(25)(26)(27). We further examined the role of the C-terminal domain of apoA-I and the lipidation of WT apoA-I on the association with different cellular compartments.…”

Section: Development Of a Quantitative Biotinylation Assay-tomentioning

confidence: 90%

Quantitative Analysis of ABCA1-dependent Compartmentalization and Trafficking of Apolipoprotein A-I

Hassan¹,

Bailey²,

Lee

et al. 2008

Journal of Biological Chemistry

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The molecular mechanisms underlying the apoA-I/ABCA1 endocytic trafficking pathway in relation to high density lipoprotein (HDL) formation remain poorly understood. We have developed a quantitative cell surface biotinylation assay to determine the compartmentalization and trafficking of apoA-I between the plasma membrane (PM) and intracellular compartments (ICCs). Here we report that 125 I-apoA-I exhibited saturable association with the PM and ICCs in baby hamster kidney cells stably overexpressing ABCA1 and in fibroblasts. The PM was found to have a 2-fold higher capacity to accommodate apoA-I as compared with ICCs. Overexpressing various levels of ABCA1 in baby hamster kidney cells promoted the association of apoA-I with PM and ICCs compartments. The C-terminal deletion of apoA-I ⌬(187-243) and reconstituted HDL particles exhibited reduced association of apoA-I with both the PM and ICCs. Interestingly, cell surface biotinylation with a cleavable biotin revealed that apoA-I induces ABCA1 endocytosis. Such endocytosis was impaired by naturally occurring mutations of ABCA1 (Q597R and C1477R). To better understand the role of the endocytotic pathway in the dynamics of the lipidation of apoA-I, a pulse-chase experiment was performed, and the dissociation (re-secretion) of 125 I-apoA-I from both PM and ICCs was monitored over a 6-h period. Unexpectedly, we found that the time required for 50% dissociation of 125 I-apoA-I from the PM was 4-fold slower than that from ICCs at 37°C. Finally, treatment of the cells with phosphatidylcholine-specific phospholipase C, increased the dissociation of apoA-I from the PM. This study provides evidence that the lipidation of apoA-I occurs in two kinetically distinguishable compartments. The finding that apoA-I specifically mediates the continuous endocytic recycling of ABCA1, together with the kinetic data showing that apoA-I associated with ICCs is rapidly re-secreted, suggests that the endocytotic pathway plays a central role in the genesis of nascent HDL.

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Section: Development Of a Quantitative Biotinylation Assay-tomentioning

confidence: 90%

Quantitative Analysis of ABCA1-dependent Compartmentalization and Trafficking of Apolipoprotein A-I

Hassan¹,

Bailey²,

Lee

et al. 2008

Journal of Biological Chemistry

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“…5). In fact, ABCG1 mediates the efflux of cholesterol to apoE-PC liposomes, 93,94) and functions in the formation of LpE. 95) Because ABCG1 and ABCG4 are also expressed in neurons, they may mediate the efflux of excess cholesterol from the neurons, though most of the excess cholesterol in the neurons is excreted after conversion to oxysterols such as 24-hydroxycholesterol.…”

Section: Functions Of Abcg1 and Abcg4 In Brainmentioning

confidence: 99%

ATP-Binding Cassette Proteins Involved in Glucose and Lipid Homeostasis

Matsuo¹

2010

Bioscience, Biotechnology, and Biochemistry

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Glucose and lipids are essential to the body, but excess glucose or lipids lead to metabolic syndrome. ATP-binding cassette (ABC) proteins are involved in the homeostasis of glucose and lipid in that they regulate insulin secretion and remove excess cholesterol from the body. Sulfonylurea receptor (SUR) is a subunit of the ATP-sensitive potassium channels, which regulate insulin secretion from pancreatic -cells by sensing cellular metabolic levels. ABCG1 removes excess cholesterol from peripheral tissues and functions in reverse cholesterol transport to the liver. ABCG5 and ABCG8 suppress the absorption of cholesterol in the intestine and exclude cholesterol from the liver to the bile duct. ABCG1 and ABCG4, expressed in the central nervous system, play roles in lipid metabolism in the brain. These ABC proteins are targets of drugs and functional foods to cure and prevent diabetes, hyperlipidemia, and neurodegenerative diseases. In this review, recent knowledge of the physiological function and regulation of ABC proteins in the homeostasis of glucose and lipids is discussed.

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“…The construct was confirmed by DNA sequencing. To generate stable U251-MG cell lines expressing human ABCA1 promoter-luciferase, the U251-MG cells seeded in 6-well plates at 7ϫ10 4 cells/well were transfected with pGL4. 14hABCA1p using FuGENE HD (Roche, Mannheim, Germany), followed by the selection of stable transfectants using 0.3 mg/ml hygromycin (Invitrogen Corp., Carlsbad, CA, U.S.A.) in the growth medium for 7 d.…”

Section: Methodsmentioning

confidence: 99%

“…2,3) ABCA1 also plays an important role in the central nervous system (CNS). Apolipoprotein E (apoE) is one of the major apolipoproteins in CNS, which interacts with ABCA1 4) to remove cholesterol from cells and generates HDL particles in the cerebrospinal fluid.…”

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confidence: 99%

Honokiol Increases ABCA1 Expression Level by Activating Retinoid X Receptor Beta

Jung

Horike

Cha

et al. 2010

Biological & Pharmaceutical Bulletin

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ABCA1, a member of the ATP-binding cassette transporter family, promotes the efflux of cholesterol and phospholipids from intracellular compartments to extracellular cholesterol acceptors.1) Mutations in the ABCA1 gene result in high-density lipoprotein (HDL) deficiency syndromes, such as Tangier disease, which is characterized by low levels of HDL cholesterol and apolipoprotein A-I (apoA-I) and an increased risk of cardiovascular disease.2,3) ABCA1 also plays an important role in the central nervous system (CNS). Apolipoprotein E (apoE) is one of the major apolipoproteins in CNS, which interacts with ABCA1 4) to remove cholesterol from cells and generates HDL particles in the cerebrospinal fluid.5) The lack of ABCA1 results in a reduction of apoE levels and lipidated apoE-containing lipoproteins in the brain of ABCA1 Ϫ / Ϫ mice.6) It has also been reported that decreased apoE levels and poorly lipidated apoE increase amyloid-b peptide (Ab), a major component of the senile plaque in Alzheimer disease (AD) brains, deposition in ABCA1 Ϫ / Ϫ mice crossed with the AD mouse model. 7) In contrast, overexpression of ABCA1 results in the reduction of Ab deposition through ABCA1-mediated generation of apoE containing lipoproteins in the AD mouse model 8) suggesting that modulation of ABCA1 expression could be a possible therapeutic strategy for AD.ABCA1 is ubiquitously expressed, the expression of which is transcriptionally regulated. The activation of liver X receptor (LXR) by oxysterols and the nonsteriodal synthetic LXR agonist T0901317 increases ABCA1 gene expression level. 9)ABCA1 is also regulated by peroxisome proliferator-activated receptors (PPARs) through their inductive effects on the expression of LXRa.10) Both of these types of receptor form heterodimers with retinoid X receptors (RXRs), 11) and LXR/RXR and PPARs/LXR heterodimers bind to a promoter sequence on the ABCA1 gene. 10,12) In mice models, the synthetic LXR agonist GW3965 increases the plasma HDL cholesterol level and inhibits the development of atherosclerosis, 13) and decrease Ab deposition in the AD mouse model. 14) Although ABCA1 plays an important role in the development of atherosclerosis and pathogenesis of AD, there are relatively few drugs that can upregulate ABCA1 expression. Thus, identification of upregulators of ABCA1 expression may lead to a therapeutic benefit for patients with cardiovascular disease and AD.Because of their simplicity and sensitivity, reporter gene assay systems are used for high-throughput screening (HTS) to identify new compounds for drug development. These strategies offer the advantages of speed, cost-effectiveness, genome coverage, and immediate biological relevance. In the present study, we have developed an HTS method of identifying ABCA1 upregulators, and screened 118 natural compounds using the developed cell-based assay. MATERIALS AND METHODS MaterialsHonokiol and rosiglitazone were purchased from LKT laboratories, Inc. (St. Paul, MN, U.S.A.) and Cayman Chemical (Ann Arbor, MI, U.S.A.), respectively. GW6471,...

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Molecular interactions between apoE and ABCA1

Cited by 115 publications

References 56 publications

Quantitative Analysis of ABCA1-dependent Compartmentalization and Trafficking of Apolipoprotein A-I

Quantitative Analysis of ABCA1-dependent Compartmentalization and Trafficking of Apolipoprotein A-I

ATP-Binding Cassette Proteins Involved in Glucose and Lipid Homeostasis

Honokiol Increases ABCA1 Expression Level by Activating Retinoid X Receptor Beta

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