ABC1 promotes engulfment of apoptotic cells and transbilayer redistribution of phosphatidylserine

• Published in: Nature cell biology Vol. 2; no. 7; pp. 399 - 406
• Main Authors: Chimini, Giovanna, Hamon, Yannick, Broccardo, Cyril, Chambenoit, Olivier, Luciani, Marie-Francoise, Toti, Florence, Chaslin, Stephane, Freyssinet, Jean-Marie, Devaux, Philippe F, McNeish, John, Marguet, Didier
• Format: Journal Article
• Language: English
• Published: England Nature Publishing Group 01.07.2000
• Subjects: Animals; Annexin A5 - metabolism; Apolipoprotein A-I - metabolism; Apolipoproteins; Apoptosis; ATP Binding Cassette Transporter 1; ATP-Binding Cassette Transporters - genetics; ATP-Binding Cassette Transporters - metabolism; Calcium - pharmacology; Cell Membrane - chemistry; Cell Membrane - metabolism; Cells, Cultured; Cholesterol; Cholesterol - metabolism; Genetic aspects; Glycoproteins - genetics; Glycoproteins - metabolism; HeLa Cells; Humans; Kinases; Lipid Bilayers - chemistry; Lipid Bilayers - metabolism; Lipids; Macrophages - cytology; Macrophages - immunology; Membrane proteins; Mice; Mice, Knockout; Phagocytosis; Phosphatidylserines; Phosphatidylserines - metabolism; Phospholipids; Physiological aspects; Recombinant Fusion Proteins - genetics; Recombinant Fusion Proteins - metabolism; RNA, Messenger - genetics; RNA, Messenger - metabolism; Spin Labels; Thromboplastin - metabolism; Thymus Gland - cytology; Transfection
• ISSN: 1465-7392; 1476-4679
• DOI: 10.1038/35017029

ATP-binding-cassette transporter 1 (ABC1) has been implicated in processes related to membrane-lipid turnover. Here, using in vivo loss-of-function and in vitro gain-of-function models, we show that ABC1 promotes Ca2+-induced exposure of phosphatidylserine at the membrane, as determined by a prothrombinase assay, membrane microvesiculation and measurement of transbilayer redistribution of spin-labelled phospholipids. That ABC1 promotes engulfment of dead cells is shown by the impaired ability of ABC1-deficient macrophages to engulf apoptotic preys and by the acquisition of phagocytic behaviour by ABC1 transfectants. Release of membrane phospholipids and cholesterol to apo-AI, the protein core of the cholesterol-shuttling high-density lipoprotein (HDL) particle, is also ABC1-dependent. We propose that both the efficiency of apoptotic-cell engulfment and the efflux of cellular lipids depend on ABC1-induced perturbation of membrane phosphatidylserine turnover. Transient local exposure of anionic phospholipids in the outer membrane leaflet may be sufficient to alter the general properties of the membrane and thus influence discrete physiological functions.