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

ATP-binding-cassette transporter 1 (ABC1) has been implicated in processes related to membrane-lipid turnover. Here, using in vivo Toss-of-function an d in vitro gain-of-function models, we show that ABC1 promotes Ca2+-induced exposure of phosphatidylserine at the membrane, as determined by a prothro mbinase assay, membrane microvesiculation and measurement of transbilayer r edistribution of spin-labelled phospholipids. That ABC1 promotes engulfment of dead cells is shown by the impaired ability of ABC1-deficient macrophag es to engulf apoptotic preys and by the acquisition of phagocytic behaviour by ABC1 transfectants. Release of membrane phospholipids and cholesterol t o apo-AI, the protein core of the cholesterol-shuttling high-density lipopr otein (HDL) particle, is also ABC1-dependent. We propose that both the effi ciency of apoptotic-cell engulfment and the efflux of cellular lipids depen d on ABC1-induced perturbation of membrane phosphatidylserine turnover. Tra nsient local exposure of anionic phospholipids in the outer membrane leafle t may be sufficient to alter the general properties of the membrane and thu s influence discrete physiological functions.