Role of plasma membrane phospholipids in the uptake and release of transferrin and its iron by reticulocytes.
The involvement of membrane phospholipids in the utilization of transferrin-bound iron by reticulocytes was investigated using [59Fe]- and [125I]-labelled transferrin and rabbit reticulocytes which had been incubated with phospholipase A. Transferrin and iron uptake and release were all inhibited by phospholipase A which produced a marked decrease in the relative abundance of phosphatidylcholine and phosphatidylethanolamine and equivalent increases in their lyso-compounds in the reticulocyte plasma membrane. There was a close correlation between the iron uptake rate and the rate and amount of transferrin uptake and the amount of the lysophospholipids in the membrane. Incubation of the cells with exogenous lysophosphatidylethanolamine or lysophosphatidylcholine also produced inhibition of iron and transferrin uptake. The reduced uptake produced by phospholipase A could be reversed if the lyso-compounds were removed by fatty acid-free bovine serum albumin or by reincubation in medium 199. Treatment with phospholipase A was shown to increase the amount of transferrin bound by specific receptors on the reticulocyte membrane but to inhibit the entry of transferrin into the cells. The present investigation provides evidence that the phospholipid composition of the cell membrane influences the interaction of transferrin with its receptors, the processes of endocytosis and exocytosis whereby transferrin enters and leaves the cells, and the mechanism by which iron is mobilized between its binding to transferrin and incorporation into heme. In addition, the results indicate that phosphatidylethanolamine is present in the outer half of the lipid bilayer of reticulocyte membrane.
D000818:Animals; D002462:Cell Membrane / Q000502:physiology* / Q000648:ultrastructure; D007501:Iron / Q000097:blood*; D008563:Membrane Lipids / Q000502:physiology*; D008854:Microscopy, Electron; D008855:Microscopy, Electron, Scanning; D010743:Phospholipids / Q000502:physiology*; D011817:Rabbits; D012156:Reticulocytes / Q000378:metabolism* / Q000648:ultrastructure; D014168:Transferrin / Q000378:metabolism*
D008563:Membrane Lipids; D010743:Phospholipids; D014168:Transferrin; D007501:Iron