{"database":"biostudies-literature","file_versions":[],"scores":null,"additional":{"submitter":["Iatan I"],"funding":["Canadian Institutes of Health Research"],"pagination":["2043-55"],"full_dataset_link":["https://www.ebi.ac.uk/biostudies/studies/S-EPMC3196236"],"repository":["biostudies-literature"],"omics_type":["Unknown"],"volume":["52(11)"],"pubmed_abstract":["Recent studies have identified an ABCA1-dependent, phosphatidylcholine-rich microdomain, called the \"high-capacity binding site\" (HCBS), that binds apoA-I and plays a pivotal role in apoA-I lipidation. Here, using sucrose gradient fractionation, we obtained evidence that both ABCA1 and [¹²⁵I]apoA-I associated with the HCBS were found localized to nonraft microdomains. Interestingly, phosphatidylcholine (PtdCho) was selectively removed from nonraft domains by apoA-I, whereas sphingomyelin and cholesterol were desorbed from both detergent-resistant membranes and nonraft domains. The modulatory role of cholesterol on apoA-I binding to ABCA1/HCBS was also examined. Loading cells with cholesterol resulted in a drastic reduction in apoA-I binding. Conversely, depletion of membrane cholesterol by methyl-β-cyclodextrin treatment resulted in a significant increase in apoA-I binding. Finally, we obtained evidence that apoA-I interaction with ABCA1 promoted the activation and gene expression of key enzymes in the PtdCho biosynthesis pathway. Taken together, these results provide strong evidence that the partitioning of ABCA1/HCBS to nonraft domains plays a pivotal role in the selective desorption of PtdCho molecules by apoA-I, allowing an optimal environment for cholesterol release and regeneration of the PtdCho-containing HCBS. This process may have important implications in preventing and treating atherosclerotic cardiovascular disease."],"journal":["Journal of lipid research"],"pubmed_title":["Membrane microdomains modulate oligomeric ABCA1 function: impact on apoAI-mediated lipid removal and phosphatidylcholine biosynthesis."],"pmcid":["PMC3196236"],"funding_grant_id":["MOP 15042"],"pubmed_authors":["Bailey D","Krimbou L","Genest J","Hafiane A","Campbell S","Ruel I","Iatan I"],"additional_accession":[]},"is_claimable":false,"name":"Membrane microdomains modulate oligomeric ABCA1 function: impact on apoAI-mediated lipid removal and phosphatidylcholine biosynthesis.","description":"Recent studies have identified an ABCA1-dependent, phosphatidylcholine-rich microdomain, called the \"high-capacity binding site\" (HCBS), that binds apoA-I and plays a pivotal role in apoA-I lipidation. Here, using sucrose gradient fractionation, we obtained evidence that both ABCA1 and [¹²⁵I]apoA-I associated with the HCBS were found localized to nonraft microdomains. Interestingly, phosphatidylcholine (PtdCho) was selectively removed from nonraft domains by apoA-I, whereas sphingomyelin and cholesterol were desorbed from both detergent-resistant membranes and nonraft domains. The modulatory role of cholesterol on apoA-I binding to ABCA1/HCBS was also examined. Loading cells with cholesterol resulted in a drastic reduction in apoA-I binding. Conversely, depletion of membrane cholesterol by methyl-β-cyclodextrin treatment resulted in a significant increase in apoA-I binding. Finally, we obtained evidence that apoA-I interaction with ABCA1 promoted the activation and gene expression of key enzymes in the PtdCho biosynthesis pathway. Taken together, these results provide strong evidence that the partitioning of ABCA1/HCBS to nonraft domains plays a pivotal role in the selective desorption of PtdCho molecules by apoA-I, allowing an optimal environment for cholesterol release and regeneration of the PtdCho-containing HCBS. This process may have important implications in preventing and treating atherosclerotic cardiovascular disease.","dates":{"release":"2011-01-01T00:00:00Z","publication":"2011 Nov","modification":"2026-05-02T14:02:49.514Z","creation":"2019-03-27T00:45:06Z"},"accession":"S-EPMC3196236","cross_references":{"pubmed":["21846716"],"doi":["10.1194/jlr.M016196","10.1194/jlr.m016196"]}}