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ABC1 promotes engulfment of apoptotic cells and transbilayer redistribution of phosphatidylserine.

Nature Cell Biology volume 2, pages 399–406 (2000)Cite this article

Abstract

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.

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Figure 1: Establishment of ABC1-null mice.
Figure 2: Engulfment defect in ABC1-null mice.
Figure 3: Generation of transfectants.
Figure 4: Subcellular localization of ABC1.
Figure 5: ABC1-expressing cells acquire the ability to engulf apoptotic thymocytes.
Figure 6: ABC1 modulates lipid efflux to the apo-AI acceptor.
Figure 7: Figure 7 ABC1 promotes transbilayer redistribution of phosphatidylserine.

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Acknowledgements

We thank H. Cremer for the pKO vector, Pfizer for support in the generation of ABC1–/– mice, Y. Yamamoto and C. Henderson for help with the whole-mount TUNEL technique, A. LeBivic and S. Meresse for antibodies against giantin, 6C4, Lamp1 and M6PR, S. Granjeaud for help with software, G. Schmitz and W. Drobnik for introducing O.C. to the techniques of lipid effluxes, and J.F. Brunet, P.Golstein, P. Henson and V. Fadok for discussions. P.D. acknowledges the excellent technical assistance of P. Herve and D. Geldwerth during preliminary lipid-scrambling experiments. C.B.and Y.H. were supported by an ARC fellowship. This work was supported by Institutional grants from INSERM and CNRS, and by specific grants from ARC, LLNC and CNRS.

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  1. Yannick Hamon, Cyril Broccardo and John McNeish: These authors contributed equally to this work

Authors and Affiliations

  1. Centre d’Immunologie INSERM-CNRS de Marseille Luminy, Marseille, 13288, France

    Yannick Hamon, Cyril Broccardo, Olivier Chambenoit, Marie-Francoise Luciani, Stephane Chaslin, Didier Marguet & Giovanna Chimini

  2. Unité 143 INSERM et Institut d’Hematologie et d’Immunologie Université Louis Pasteur,, Strasbourg, 67085, France

    Florence Toti & Jean-Marie Freyssinet

  3. Institut de Biologie Physico-Chimique, Paris , 75005, France

    Philippe F. Devaux

  4. Pfizer Central Research, Groton, 06340, Connecticut, USA

    John McNeish

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Correspondence to Giovanna Chimini.

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Hamon, Y., Broccardo, C., Chambenoit, O. et al. ABC1 promotes engulfment of apoptotic cells and transbilayer redistribution of phosphatidylserine.. Nat Cell Biol 2, 399–406 (2000). https://doi.org/10.1038/35017029

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