Phosphatidylserine Shedding from RBCs – A Mechanism of Membrane Modulation and Damage Control

Abstract

Normally, phospholipids (PLs) are distributed across the membrane of all cells, including the RBCs, asymmetrically [1]: aminophospholipids such as phosphatidylserine (PS) are mainly localized in the cytoplasmic leaflet of the membrane, whereas lipids with a choline head (e.g., phosphatidylcholine) are mainly localized in the outer leaflet [2]. The PS distribution across the cell membrane is in a dynamic equilibrium; while the enzyme aminophospholipid translocase inserts it inward, the scramblase causes its externalization. Some of this external PS is shed into the extracellular medium either as membrane-bound vesicles [3] or as membrane-free PS [4]. In RBCs, exposed PS is one of the signals of senescence, mediating the removal of old or damaged RBCs from the circulation [5]. Shedding of PS may reduce this signal and thus function to moderate RBC removal [6]. PS externalization and shedding are also associated with development of RBCs in the bone marrow, fulfilling various structural and functional purposes [7]. In the present review I we summarize our studied on changes in PS distribution and shedding during maturation and ageing of erythroid cells.