Phospholipid asymmetry during erythropoiesis. A study on Friend erythroleukemic cells and mouse reticulocytes

Abstract

The distribution of phospholipids over the outer and inner layers of the plasma membranes of differentiated Friend erythroleukemic cells (Friend cells) and mouse reticulocytes has been determined. Phosphatidylcholine, phosphatidylethanolamine and phosphatidylinositol were found to be distributed symmetrically over both layers, sphingomyelin was found to be enriched in the outer layer (80-85%) and phosphatidylserine appeared to be present mainly in the inner layer (80-90%) of the plasma membranes of differentiated Friend cells. The outer layer of reticulocyte membranes contains 50-60% of the phosphatidylcholine, 20% of the phosphatidylethanolamine, 82-85% of the sphingomyelin and 40-42% of the phosphatidylinositol. All of the phosphatidylserine is present in the inner layer. The results show, that the asymmetric distribution of phospholipids, typical for erythrocyte membranes, is partially apparent already at an early stage of erythropoiesis, the proerythroblast, while the final organization of phospholipid distribution takes place at some stage during enucleation of the enormoblast and release of the reticulocyte into the blood stream.

Differentiation-dependent expression of phosphatidylserine in mammalian plasma membranes: quantitative assessment of outer-leaflet lipid by prothrombinase complex formation.

“…However, as shown in Table 2, reasonable assessments of cell surface area can be obtained by determining the amount of cellular lipid. Since the fraction of total cell lipid comprising the plasma membrane of MELC is known (34) Although we have no evidence for the fate of the outer-leaflet PS, it could be relocated to its normal inner-leaflet location or removed from the cell during enucleation (36). Indeed, the asymmetrical distribution of PS is already established in the emerging reticulocyte (36).…”

“…Since the fraction of total cell lipid comprising the plasma membrane of MELC is known (34) Although we have no evidence for the fate of the outer-leaflet PS, it could be relocated to its normal inner-leaflet location or removed from the cell during enucleation (36). Indeed, the asymmetrical distribution of PS is already established in the emerging reticulocyte (36). The decrease in the amount of PS from the outer leaflet of dMELC coincides with other membrane rearrangements that occur upon differentiation (18).…”

Differential gene expression during terminal erythroid differentiation

“…Mature erythrocytes exhibit asymmetric distribution of lipids between the inner and outer leaflets of their plasma membranes [32]. The asymmetry becomes pronounced around the time that nuclear extrusion and reticulocyte formation take place [33,34]. Interestingly, up-regulation of several genes in the apolipoprotein L gene locus in humans are associated with the development of schizophrenia [35] and erythrocytes from schizophrenic patients have been shown to be deficient in a number of fatty acids compared to controls [36,37].…”

Asymmetric distribution of phospholipids in the membrane of vesicles released during in vitro maturation of guinea pig reticulocytes: Evidence precluding a role for “aminophospholipid translocase”

“…It should be noted that the flipping rate of the four spin-labeled phospholipids was about twofold higher in reticulocytes than in erythrocytes. 2) On the other hand, it has been unequivocally established that erythrocyte (Op den Kamp, 1979;Etemadi, 1980) and reticulocyte (Van der Schaft et al, 1987a) membranes have substantially the same phospholipid distribution.To answer the two above-mentioned questions, the lipid composition and phospholipid transverse distribution in the vesicle membrane were investigated and the translocation rate of spin-labeled analogues measured. The present report describes a n asymmetric phospholipid distribution in the exosome membrane that does not result from translocase activity but is due probably to vesicle size or to a specific 1ipicVprotein interaction.…”

“…It should be noted that the flipping rate of the four spin-labeled phospholipids was about twofold higher in reticulocytes than in erythrocytes. 2) On the other hand, it has been unequivocally established that erythrocyte (Op den Kamp, 1979;Etemadi, 1980) and reticulocyte (Van der Schaft et al, 1987a) membranes have substantially the same phospholipid distribution.…”