Membrane rafts

Recently, due to increased interest in membrane raft domains, extensive attention has been paid to the cholesterol-dependent liquid-ordered phase in the membrane (Subczynski and Kusumi 2003). The pulse EPR spin-labeling DOT method detected two coexisting phases in the DMPC/cholesterol membranes the liquid-ordered and the liquid-disordered domains above the phase-transition temperature (Subczynski et al. 2007b). However, using the same method for DMPC/lutein (zeaxanthin) membranes, only the liquid-ordered-like phase was detected above the phase-transition temperature (Widomska, Wisniewska, and Subczynski, unpublished data). No significant differences were found in the effects of lutein and zeaxanthin on the lateral organization of lipid bilayer membranes. We can conclude that lutein and zeaxanthin—macular xanthophylls that parallel cholesterol in its function as a regulator of both membrane fluidity and hydrophobicity—cannot parallel the ability of cholesterol to induce liquid-ordered-disordered phase separation. 

Li, Q. et al., Docosahexaenoic acid changes lipid composition and interleukin-2 receptor signaling in membrane rafts, J Lipid Res, 46, 1904, 2005. 

Chan, H.T., Hughes, D., French, R.R., Tutt, A.L., Walshe, C.A., Peeling, J.L., Glennie, M.J., and Cragg, M.S., CD20-induced lymphoma cell death is independent of both caspases and its redistribution into triton X-100 insoluble membrane rafts. Cancer Res., 63, 5480-5489, 2003. 

Recent studies showed that ASM specifically associates with phosphatidyhnositol-3-kinase (PI-3-K) upon NGF stimulation of PC 12 cells via TrkA (Bilderback et al, 2001). Association between the two molecules was mediated by the regulatory p85 subunit of PI-3-K and was restricted to membrane rafts. Activation of PI-3-K by NGF triggering resulted in an approximately 50% reduction of ASM activity pointing to a negative regulation of ASM by this mechanism. 

Grassme, H., JeHe, A., Riehle, A., Schwarz, H., Berger, J., Sandhoff, K., Kolesnick, R. and Gulbins, E., 2001a, CD95 signaling via ceramide-rich membrane rafts. J. Biol. Chem. 276 20589-20596... 

Grassme, H., Jendrossek, V., Bock, J., Riehle, A. and Gulbins E., 2001b, Ceramide-iich Membrane Rafts Mediate CD40 Clustering. J. Immunol., in press... 

Figure 1. Ceramide mediated apoptosis signaling, Recent investigations hypothesize that, at least for drug induced apoptosis, the src kinase Lyn is activated and recruited to plasma membrane rafts. There it binds to and activates a neutral sphingomyelinase (SMase) within minutes. This initial rise in ceramide levels initiates an apoptotic cascade. Howevo- several cellular events can inhibit ceramide production (by blocking sphingomyelinase activation or clearing out ceramide accumulation through increased metabolisation) and therefore contribute to cellular resistance/survival.

Nisole S, Krust B, Hovanessian AG (2002a) Anchorage of HIV on Permissive Cells Leads to Coaggregation of Viral Particles with Surface Nucleolin at Membrane Raft Microdomains. Exp Cell Res... 

Margineanu, A., Hotta, J., Auweraer, M. V. D., Ameloot, M., Stefan, A., Beijonne, D., Engleborghs, Y., et al. 2007. Visuahzation of membrane rafts using a perylene monoimide derivative and fluorescence hfetime imaging. Biophys. J. 93 2877-91. 

Membrane/rafts Bile acids Steroid hormones Lipoproteins protein modification... 

Sphingolipids and Cholesterol Cluster Together in Membrane Rafts... 

In atomic force microscopy (AFM), the sharp tip of a microscopic probe attached to a flexible cantilever is drawn across an uneven surface such as a membrane (Fig. 1). Electrostatic and van der Waals interactions between the tip and the sample produce a force that moves the probe up and down (in the z dimension) as it encounters hills and valleys in the sample. A laser beam reflected from the cantilever detects motions of as little as 1 A. In one type of atomic force microscope, the force on the probe is held constant (relative to a standard force, on the order of piconewtons) by a feedback circuit that causes the platform holding the sample to rise or fall to keep the force constant. A series of scans in the x and y dimensions (the plane of the membrane) yields a three-dimensional contour map of the surface with resolution near the atomic scale—0.1 nm in the vertical dimension, 0.5 to 1.0 nm in the lateral dimensions. The membrane rafts shown in Figure ll-20b were visualized by this technique. 

Membrane Rafts and Caveolae May Segregate Signaling Proteins... 

Membrane rafts and caveolae sequester groups of signaling proteins in small regions of the plasma membrane, enhancing their interactions and making signaling more efficient. 

Includes a description of membrane rafts and microdomains within membranes, and a new box on the use of atomic force microscopy to visualize them. 

Now covers the roles of membrane rafts and caveolae in signaling pathways, including the activities of AKAPs (A Kinase Anchoring Proteins) and other scaffold proteins... 

Gousset K, Wolkers WF, Tsvetkova NM, Oliver AE, Field CL, Walker NJ, Crowe JH, Tablin F. 2002. Evidence for a physiological role for membrane rafts in human platelets. J Cell Physiol 190 117-128. 

Sehgal PB, Guo GG, Shah M, Kumar V, Patel K. Cytokine signaling STATS in plasma membrane rafts. J Biol Chem 2002 277 12067-12074. 

Rietveld A, Simons K (1998) The differential miscibility of lipids as basis for the formation of functional membrane rafts. Biochim Biophys Acta 1376 467-479 Saitou M, Furuse M, Saski H, Schulzke JK, Fromm M, Takano H, Noda T, Tsukita S (2000) Complex phenotype of mice lacking occludin, a component of tight junction strands. Mol Biol Cell 11 4131-4142... 

Brown, D. A. and London, E. (2000). Structure and function of sphingolipid- and cholesterol-rich membrane rafts. ]. Biol. Chem. 275(23), 17221-17224. 

Altered trafficking of molecules through the endolysosomal network, including sequestration of membrane rafts, leading to a disruption in signaling... 

Integrins associate with the membrane protein caveolin.34 Although little is yet known about this particular interaction, it could assist in forming integrin clusters at the plasma membrane which might serve as a scaffold for the assembly of multi-component signalling complexes. This possibility is attractive, because caveolin binds cholesterol and glycosphingolipids and forms membrane rafts , enriched in myristoylated and palmitoy-lated Src-family kinases (Chapter 8).35... 

Plowman, S.J., Muncke, C., Parton, R.G., and Hancock, J.F. (2005). H-ras, K-ras, and inner plasma membrane raft proteins operate in nanoclusters with differential dependence on the actin cytoskeleton. Proc Natl Acad Sci USA 102 15500-15505. 

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