Molecular and Cellular Physiology of Apolipoprotein A-I Lipidation by the ATP-binding Cassette Transporter A1 (ABCA1)

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

doi:10.1074/jbc.m306963200

Cited by 89 publications

(99 citation statements)

References 45 publications

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“…Importantly, a period of 45 min of incubation of 125 I-apoA-I with cells at 37°C was chosen to permit sufficient time for equilibration of apoA-I with different cellular compartments. Although several groups used binding at 4°C to determine the association of apoA-I with the PM, we obtained evidence that incubation at 4°C alters the association of apoA-I with ABCA1 at the PM (data not shown), in agreement with previous studies (20,21). These results underscore the importance of using physiological temperatures to study apoA-I/ABCA1 interactions.…”

Section: Development Of a Quantitative Biotinylation Assay-tosupporting

confidence: 81%

“…6D) as we have previously documented (17,20). Noninduced BHK cells were unable to form such particles (data not shown).…”

Section: Development Of a Quantitative Biotinylation Assay-tosupporting

confidence: 56%

“…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: 99%

“…Analysis of Nascent ApoA-I-containing Particles-125 IApoA-I released to the medium at the time point (6 h) from mifepristone-induced BHK-ABCA1 cells was analyzed by twodimensional PAGGE, and the number of apoA-I molecules per particle was assessed by cross-linking with dithiobis(succinimidyl propionate), as described previously (20).…”

Section: Dissociation Of 125mentioning

confidence: 99%

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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-tosupporting

confidence: 81%

“…6D) as we have previously documented (17,20). Noninduced BHK cells were unable to form such particles (data not shown).…”

Section: Development Of a Quantitative Biotinylation Assay-tosupporting

confidence: 56%

Section: Development Of a Quantitative Biotinylation Assay-tomentioning

confidence: 99%

Section: Dissociation Of 125mentioning

confidence: 99%

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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 complex protein A-Sepharose-ABCA1 (25 l) was added to PKA reaction buffer containing 20 M ATP, ApoA-I Binding Assay-ApoA-I binding assay was performed as we have described previously (20) with minor modification. Briefly, purified human plasma apoA-I was iodinated with 125 I by IODO-GEN (Pierce) to a specific activity of 800 -1200 cpm/ng of apoA-I.…”

Section: Methodsmentioning

confidence: 99%

Apolipoprotein A-I Activates Cellular cAMP Signaling through the ABCA1 Transporter

Haidar

Denis

Marcil

et al. 2004

Journal of Biological Chemistry

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It has been suggested that the signal transduction pathway initiated by apoA-I activates key proteins involved in cellular lipid efflux. We investigated apoA-Imediated cAMP signaling in cultured human fibroblasts induced with (22R)-hydroxycholesterol and 9-cis-retinoic acid (stimulated cells). Treatment of stimulated fibroblasts with apoA-I for short periods of time (<45 min) increased ATP binding cassette A1 (ABCA1) phosphorylation in a concentration-dependent manner. Concomitantly, apoA-I increased the intracellular level of cAMP in a concentration-and time-dependent manner. The maximal cAMP level was reached within 10 min at 10 g/ml apoA-I representing a 1-fold increase. The ability of apoA-I to mediate cAMP production was only observed in stimulated fibroblasts. Furthermore, overexpression of ABCA1 in Chinese hamster ovary cells resulted in a 1.5-fold increase in apoA-I-mediated cAMP accumulation as compared with untransfected cells. In contrast, forskolin increased cAMP production significantly in unstimulated fibroblasts as well as in untransfected Chinese hamster ovary cells. Pharmacological inhibition of protein kinase A (H89) completely blocked apoA-I-mediated ABCA1 phosphorylation. Naturally occurring mutations of ABCA1 associated with Tangier disease (C1477R, 2203X, and 2145X) severely reduced apoA-I-mediated cAMP production, ABCA1 phosphorylation, 125 I-apoA-I binding, and lipid efflux, without affecting forskolin-mediated cAMP elevation. In contrast, the protein kinase A catalytic subunit was able to phosphorylate ABCA1 similarly from mutant and normal cell lines in vitro. Together, our results indicate that apoA-I activates ABCA1 phosphorylation through the cAMP/ protein kinase A-dependent pathway, apoA-I-mediated cAMP production required high level expression of functional ABCA1, and Tangier disease mutants have defective apoA-I-mediated cAMP signaling. These findings suggest that apoA-I may activate cAMP signaling through G protein-coupled ABCA1 transporter.

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Genetics of High‐Density Lipoproteins

Genest¹,

Dastani²,

Engert³

et al. 2007

High‐Density Lipoproteins

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Molecular and Cellular Physiology of Apolipoprotein A-I Lipidation by the ATP-binding Cassette Transporter A1 (ABCA1)

Cited by 89 publications

References 45 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

Apolipoprotein A-I Activates Cellular cAMP Signaling through the ABCA1 Transporter

Genetics of High‐Density Lipoproteins

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