Lipid rafts sphingomyelin

Cholesterol is an important structural component of cellular membranes, where it plays a role in modulating membrane fluidity and phase transitions, and, together with sphingomyelin, forms lipid rafts or caveolae, which are sites where proteins involved in diverse signaling pathways become concentrated. Furthermore, cholesterol is a precursor of oxysterols, steroid hormones, and bile acids. 

C. Yuan, J. Furlong, P. Burgos and L. J. Johnston, The size of lipid rafts an atomic force microscopy study of ganglioside GM1 domains in sphingomyelin/ DOPC/cholesterol membranes, Biophys. J., 82 (2002) 2526-2535. 

Figure 5 Snapshot of a lipid raft system studied through atomistic molecular dynamics simulations (42). Water is shown at the top and at the bottom in light color, while the membrane is in the middle of the figure. In the bilayer, rigid cholesterol molecules are shown in light grey, POPC in dark grey, and sphingomyelin in intermediate grey.

The results of recent studies have challenged the long-held belief that lipids are randomly mixed in each leaflet of a bilayer. The first hint that lipids may be organized within the leaflets was the discovery that the residues remaining after the extraction of plasma membranes with detergents contain two lipids cholesterol and sphingomyelin. Because these two lipids are found in more ordered, less fluid bilayers, researchers hypothesized that they form microdomains, termed lipid rafts, surrounded by other more fluid phospholipids that are easily extracted by detergents. 

Van der Luit, A.H., Budde, M., Zerp, S., Caan, W., Klarenbeek, J.B., Verheij, M., and Van Blitterswijk, W.J. Resistance to alkyl-lysophospholipid-induced apoptosis due to down-regulated sphingomyelin synthase 1 expression with consequent sphingomyelin- and cholesterol-deficiency in lipid rafts. Biochem J, 401, 2007, 541-549. 

Lipid rafts (flotillin, LBPA, cholesterol, sphingomyelin)... 

An NMR-based conformational analysis which also included /hh couplings has been performed by Murata and co-workers for sphingomyelin in bicells, a common sphingolipid in mammalian membranes involved in the formation of lipid rafts. 

Matsumori et al. have observed that fluorinated cholesterol retains lipid microdomain-forming activity in sphingomyelin bilayers and therefore can be used as a molecular probe for understanding molecular recognition in lipid rafts. The effects of cholesterol on phospholipid membranes made of... 

Prieto, M., Sphingomyelin/ Phosphatidylchohne/ Cholesterol Phase Diagram Boundaries and Composition of Lipid Rafts, 2406-2416, Copyright (2003), with permission from Elsevier [5]... 

Sphingomyelin (SM) A Hpid with a phosphocholine group linked to a ceramide shares the same head group as phosphatidylcholine (PC) but displays different physicochemical properties. SM and PC do not normally mix in biological membranes, because SM is associated with cholesterol in plasma membrane microdomains such as lipid rafts. 

Lipid rafts are lateral structural components of the plasma membrane enriched with cholesterol (Choi) and sphingomyelin (SM), onto which specific proteins attach within the bilayers. Lipid mixtures consisting of Choi, phosphatidylcholine (PC), and SM have often been used to mimic the rafts in cells. It is well established that this mixture gives rise to coexisting liquid-ordered (Lo) domains (SM/Chol-enriched) and liquid-disordered (Ld) phase (PC-enriched) in the bilayers. " " ... 

FIGURE 10.12 The mole ratio of carotenoid/phospholipid and carotenoid/total lipid (phospholipid + cholesterol) in raft domain (detergent-resistant membrane, DRM) and bulk domain (detergent-soluble membrane, DSM) isolated from membranes made of raft-forming mixture (equimolar ternary mixture of dioleoyl-PC (DOPC)/sphingomyelin/cholesterol) with 1 mol% lutein (LUT), zeaxanthin (ZEA), P-cryptoxanthin (P-CXT), or P-carotene (P-CAR). 

Epand RM, Epand RE. Non-raft forming sphingomyelin-cholesterol mixtures. Chem. Phys. Lipids 2004 132 37-46. 

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