Lipid Asymmetry and Transport


 
A remarkable feature of several biological membrane systems is that their phospholipids are asymmetrically distributed across the lipid bilayer, a phenomenon called membrane phospholipid asymmetry. Most of our knowledge on phospholipid asymmetry of lipids has come from studies on human erythrocytes. The aminophospholipids, phosphatidylethanolamine (PE) and in particular phosphatidylserine (PS) are preferentially located in the inner leaflet of the membrane bilayer, while the other major components sphingomyelin (SM) and phosphatidylcholine (PC) are more abundant in the outer leaflet. It is assumed that phospholipids are also distributed asymmetrically in the plasma membrane of most, if not all, nucleated cells. Three distinct mechanisms for transmembrane movement of phospholipids have been described: (i) spontaneous diffusion (ii) facilitated diffusion and (iii) ATP-dependent, active translocation (Fig.1). Active transport
ATP-dependent
(e.g. Aminophospholipid-translocase for PS+PE
in plasma membrane)
Spontanous diffusion
ATP-independent
Plasma membrane phospholipid asymmetry plays a crucial role in a variety of biological processes . Fig.1 Mechanisms of Lipid transmembrane movement
Most of our current knowledge on the kinetics of phospholipid transmembrane movement in cell membranes has been gained using phospholipid analogues in translocation assays.  
The information gleaned from those translocation assays has been used to formulate mathematical models which allow calculation of the transmembrane movement and distribution of phospholipids.  
 
Results and Conclusions:
 
  Transmembrane movement of phospholipids in the plasma membrane of myoblasts
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  Translocation of phospholipids in the plasma membrane of sperm cells
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  Redistribution of phospholipids in the plasma membrane of fibroblasts
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  Translocation of phospholipids in the plasma membrane of hepatocytes
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  Transmembrane movement of phospholipids in the plasma membrane of yeast cells
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  Relevance of phospholipid asymmetry in endocytosis
 
  In order to investigate the relevance of the aminophospholipid translocase and transverse phospholipid distribution in endocytosis of mammalian cells, the invagination of human erythrocyte ghosts and , subsequently, endocytic like vesiculation in the presence of high concentrations of ATP has been measured. After incorporation of spin-labeled phospholipid analogues (PC, SM or PS) into the outer leaflet a decline of endocytic vesiculation was observed. Suppression was arrested after about 20 minutes when ghosts have been labeled with the PS analogue known to redistribute rapidly to the inner leaflet mediated by the aminophospholipid translocase. These data suggest that vesiculation of erythrocyte ghosts is affected by differential expansion of the inner and outer leaflet. ...back