Phospholipid asymmetry

Zwaal R. F. A., Schroit A. J. Pathophysiologic implications of membrane phospholipid asymmetry in blood cells. Blood 1997 89, 1121-32. 

The properties of membranes commonly studied by fluorescence techniques include motional, structural, and organizational aspects. Motional aspects include the rate of motion of fatty acyl chains, the head-group region of the phospholipids, and other lipid components and membrane proteins. The structural aspects of membranes would cover the orientational aspects of the lipid components. Organizational aspects include the distribution of lipids both laterally, in the plane of the membrane (e.g., phase separations), and across the membrane bilayer (phospholipid asymmetry) and distances from the surface or depth in the bilayer. Finally, there are properties of membranes pertaining to the surface such as the surface charge and dielectric properties. Fluorescence techniques have been widely used in the studies of membranes mainly since the time scale of the fluorescence lifetime coincides with the time scale of interest for lipid motion and since there are a wide number of fluorescence probes available which can be used to yield very specific information on membrane properties. 

Reviews of membrane phospholipid asymmetry in health (Zachowski, 1993) and disease (Zwaal and Schroit, 1997) have been published. This chapter will be concerned with the process whereby the asymmetric... 

Methods used to demonstrate the existence of membrane phospholipid asymmetry, such as chemical labelling and susceptibility to hydrolysis or modification by phospholipases and other enzymes, are rmsuitable for dynamic studies because the rates of chemical and biochemical reactions are of a different order compared to the transmembrane translocahon of the phospholipids. Indirect methods have therefore been developed to measure the translocation rate which are consequent on the loss of membrane phospholipid asymmetry. Thus time scales appropriate to rates of lipid scrambling under resting conditions or when the forces preserving the asymmetric phospholipid distribution are disturbed can be monitored. Generally the methods rely on detecting the appearance of phosphatidylserine on the surface of cells. Methods of demonstrating Upid translocation in mammalian cells has been the subject of a recent review (Bevers etal., 1999). 

The loss of membrane phospholipid asymmetry is known to be an important signaling mechanism. As will be discussed below, the consequences of appearance of specific phospholipids on opposite sides of the membrane triggers a variety of cellular responses. 

Reviews of the role of aminophospholipid translocase and scramblase (Schlegel et al, 2000) and the consequences of the appearance of phosphatidylserine on the cell surface (Williamson et al, 2001) in apoptosis of thymocytes have been published. The precise relationship between membrane phospholipid asymmetry and apoptosis is currently a topic of considerable interest. 

Verkleij, A.J. and Post, J.A., 2000, Membrane phospholipid asymmetry and signal transduction. J. Memb. Biol. 178 1-10. 

Fadok, V.A., deCathehneau, A., Daleke, D.L., Henson, P.M., and Bratton, D.L., 2001, Loss of phospholipid asymmetry and surface exposure of phosphatidylserine is required for phagocytosis of apoptotic cells by macrophages and fibroblasts, 7. Biol. Chem. 276 1071-1077. 

Daleke, D.L. Regulation of transbilayer plasma membrane phospholipid asymmetry. J. Lipid Res. 

Intermediate-level review of phospholipid asymmetry and factors that influence it. 

Zwaal RFA, Bevers EM, Comfurius P Rosing J, Tilly RHJ, Verhallen PFJ. Loss of membrane phospholipid asymmetry during activation of blood platelets and sickled red cells mechanisms and physiological significance, Mol Cell Biochem 1989 91 23-3 I. 

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