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
An active translocation of phospholipids by an ATP-dependent ‘aminophospholipid translocase’ was first described for the plasma membrane of human erythrocytes (Seigneuret M. and P.F. Devaux, 1984, Proc. Natl. Acad. Sci. USA 81: 3751-3755). Later aminophospholipid translocase activity was also found in the plasma membrane of nucleated cells. Aminophospholipid translocase rapidly moves phosphatidylserine (PS) and phosphatidylethanolamine (PE) form the exoplasmic membrane leaflet to the cytoplasmic leaflet, on condition that the cells contain ATP as an energy source. The same specific movement of PS and PE was later described in plasma membranes from other cells, namely fibroblasts, sperm cells, myoblasts and hepatocytes. The reaction is inhibited by vanadate and fluoride, which argues strongly in favour of the involvement of a P-type ATPase. There are several pieces of evidence that the activity of the aminophospholipid translocase is responsible for the maintenance and perhaps for the origin of the transverse asymmetric distribution of phospholipids in eukaryotic plasma membranes. Attempts to identify the aminophospholipid translocase of human erythrocytes were not really successful so far. Two candidate proteins were put forward, a 110 kDa ATPase and a polypeptide of 32 kDa. Most importantly the gene coding for the translocase of human erythrocytes has not been cloned yet. A major breakthrough in the identification of an aminophospholipid translocase was made in 1996, when the gene encoding the ATPase II of bovine chromaffin cells was cloned (Tang X. et al., 1996, Science 272: 1495-1497). The ATPase II belongs to an ancient subfamily of P-type ATPases that also includes the product of the DRS 2 gene in yeast cells. ...back
Plasma membrane phospholipid asymmetry plays a crucial role in a variety of biological processes .  
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
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