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
Interest in the biological significance of membrane asymmetry has been catalyzed by studies which have shown that the loss of the asymmetry plays an important role in the process of platelet activation and blood clotting. Activation of blood platelets rapidly results in the exposure of anionic phospholipids, particularly phosphatidylserin (PS), on the surface of the platelets, thereby activating the prothrombinase complex. Furthermore, exposure of PS on the outer surface of aged erythrocytes serves as a signal triggering macrophage recognition. Apoptotic cells expose high amounts of PS on the exoplasmic plasma membrane leaflet, whereas in cells that are not undergoing apoptosis PS is almost totally confined to the cytoplasmic leaflet of the plasma membrane. Recognition of aged erythrocytes and apoptotic cells by macrophages could be related to a loss of membrane asymmetry and exposure of PS on the exoplasmic leaflet. Another possible function of an asymmetric lipid distribution could be the modulation of enzyme activities. Many proteins in the cytosol bind to the plasma membrane through interaction with charged phospholipids such as phosphatidic acid (PA), phosphatidylinositol (PI) and PS. For example, protein kinase C activity strongly depends upon PS concentration. ...back
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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