Cell surface exposure of phosphatidylserine during apoptosis is phylogenetically conserved

Abstract

Exposure of the aminophospholipid phosphatidylserine at the outer leaflet of the plasma membrane by apoptotic cells can trigger phagocytic removal of these dying cells. This functionality of phosphatidylserine exposure in the process of phagocytosis is indicated by in vitro studies of mammalian and insect phagocytes. We have studied the in vivo distribution of cell-surface exposed phosphatidylserine by injecting biotinylated Annexin V, a Ca2+ -dependent phosphatidyl-serine binding protein, into viable mouse and chick embryos and Drosophila pupae. The apparent binding of Annexin V to cells with a morphology which is characteristic of apoptosis and which was present in regions of developmental cell death indicates that phosphatidylserine exposure by apoptotic cells is a phylogenetically conserved mechanism.

Phosphatidylserine, a death knell

“…Non-apoptotic cells of all types were generally unlabeled, indicating that their PS was not exposed on the outer leaflet of the plasma membrane and thus neatly demonstrating the ubiquity of PS asymmetry. Similar experiments in chick and Drosophila embryos confirm that most normal cells in these animals also sequester PS, 42 arguing that plasma membrane lipid asymmetry was a property of the cells of the common ancestor of vertebrates and invertebrates, which lived sometime in the Precambrian, over 600 million years ago. Notably, two instances of annexin binding by non-apoptotic cells were observed: myoblasts fusing to form myotubes and myocardioblasts to form cardiac muscle, and megokaryoblasts and megakaryocytes from which thrombocytes were forming.…”

NADPH Oxidase-dependent Oxidation and Externalization of Phosphatidylserine during Apoptosis in Me2SO-differentiated HL-60 Cells

“…This removal takes place through recognition of apoptotic neutrophils by phagocytes via a pathway that involves exposure of PS on neutrophil cell surfaces (1)(2)(3)(4)(5)(6)). Yet the mechanisms underlying apoptosis in activated neutrophils, particularly those involving PS externalization, are not fully characterized.…”

“…To prevent calamitous release of ROS, macrophages remove excess activated neutrophils from an inflammatory site in a regulated way, through processes that ensure swift resolution of inflammation yet make provision for neutrophils to fulfill their microbicidal function. Phagocytic cells carry out this clearance by recogniz-ing apoptotic neutrophils through a mechanism that involves the exposure of phosphatidylserine (PS) on the neutrophil cell surface (1)(2)(3)(4)(5)(6).…”

Molecular mechanisms of cell death and phagocytosis in Drosophila

“…82,90 Other receptors that may play a role in the recognition of apoptotic cells in the embryo are the Drosophila phosphatidylserine (PS) receptor, 93 and the Drosophila scavenger receptor, DSR-CI. 94 PS exposure is a common feature of apoptotic death, 95 and a recently identified mammalian PS receptor appears to be both necessary and sufficient to promote the engulfment of apoptotic corpses in some cell types. 93 The Drosophila homologue is highly conserved, but its function has not yet been characterized.…”