title: ABCA1 and nascent HDL biogenesis.
abstract: ABCA1 mediates the secretion of cellular free cholesterol and phospholipids to an extracellular acceptor, apolipoprotein AI, to form nascent high-density lipoprotein (HDL). Thus, ABCA1 is a key molecule in cholesterol homeostasis. Functional studies of certain Tangier disease mutations demonstrate that ABCA1 has multiple activities, including plasma membrane remodeling and apoAI binding to cell surface, which participate in nascent HDL biogenesis. Recent advances in our understanding of ABCA1 have demonstrated that ABCA1also mediates unfolding the N terminus of apoAI on the cell surface, followed by lipidation of apoAI and release of nascent HDL. Although ABCA1-mediated cholesterol efflux to apoAI can occur on the plasma membrane, the role of apoAI retroendocytosis during cholesterol efflux may play a role in macrophage foam cells that store cholesterol esters in cytoplasmic lipid droplets.
authors.affiliation: Department of Cellular and Molecular Medicine, Cleveland Clinic, Cleveland, OH.
authors.forename: Shuhui
authors.initials: S
authors.lastname: Wang
authors.forename: Jonathan D
authors.initials: JD
authors.lastname: Smith
mesh_terms: D064286:ATP Binding Cassette Transporter 1 / Q000235:genetics / Q000378:metabolism*; D000818:Animals; D016632:Apolipoprotein A-I / Q000235:genetics / Q000378:metabolism*; D050197:Atherosclerosis / Q000235:genetics / Q000378:metabolism* / Q000473:pathology; D001692:Biological Transport; D002462:Cell Membrane / Q000737:chemistry / Q000378:metabolism; D002788:Cholesterol Esters / Q000378:metabolism; D005786:Gene Expression Regulation; D006706:Homeostasis; D006801:Humans; D066292:Lipid Droplets / Q000737:chemistry / Q000378:metabolism; D050356:Lipid Metabolism; D008075:Lipoproteins, HDL / Q000096:biosynthesis* / Q000097:blood; D015398:Signal Transduction; D013631:Tangier Disease / Q000235:genetics / Q000378:metabolism* / Q000473:pathology
chemical_list: C577836:ABCA1 protein, human; D064286:ATP Binding Cassette Transporter 1; D016632:Apolipoprotein A-I; D002788:Cholesterol Esters; D008075:Lipoproteins, HDL
keywords: ABCA1; apoAI; atherosclerosis; high-density lipoprotein; reverse cholesterol transport