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

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.

P2X7 receptors regulate multiple types of membrane trafficking responses and non-classical secretion pathways

“…Neutrophils stimulated with chemotactic peptides, such as formylated Met-Leu-Phe (fMLP), exhibit transient cell surface PS expression [10]. Macrophages per se undergo membrane PS flip during their recognition and phagocytosis of dead cells [11][12][13][14]. Similarly, rapid changes in cell surface PS triggered by the natively expressed P2X7R in various leukocyte types have been associated with physiological signal transduction.…”

UV irradiation inhibits ABC transporters via generation of ADP-ribose by concerted action of poly(ADP-ribose) polymerase-1 and glycohydrolase

“…6 Furthermore, ABC1 was shown to be involved in engulfment of apoptotic cells. 7,8 One of the physiological roles of ABC transporters is detoxification by extrusion of various toxic compounds from the cytoplasm. [9][10][11] Detoxification is particularly crucial when cell injury occurs.…”

Macrophage-mediated clearance of cells undergoing caspase-3-independent death

“…9 On the side of the macrophage, a growing body of evidence indicates that a variety of receptors of diverse structure are involved in apoptotic-cell removal. These include (i) CD14, 10 (ii) a novel PS-receptor, 11 (iii) the integrin a v b 3 , 12,13 (iv) CD36, 13,14 (v) the class A scavenger receptor SR-A, 15 (vi) the ATP-binding cassette transporter, ABC-1, 16,17 (vii) the receptor tyrosine kinase, MER 18 and (viii) the a-2-macroglobulin receptor, CD91. 19 Additional molecules, notably thrombospondin, 13 Clq, 19,20 mannose-binding lectin, calreticulin 19 and C-reactive protein 21 may serve as intermediates that bridge macrophage and apoptotic-cell surfaces or act as opsonins.…”