Lipid raft

Early descriptions of lipid rafts noted their enrichment in cholesterol and glycosph-ingolipids and focused on their ability to resist extraction by nonionic detergents [32]. Later experiments showed that lipid rafts were a heterogeneous collection of domains that differ in protein and lipid composition as well as in temporal stability [33, 34]. The distinctive lipid composition of membrane rafts as demonstrated by lipidomics makes a clearer picture of membrane rafts. 

Cholesterol levels in rafts were generally double from those found in their derived plasma membranes [35]. Similarly, the levels of SM species in the rafts were elevated by approximately 50% in comparison to that present in plasma membranes [35, 36]. Intriguingly, the elevated SM levels were offset with the decreased levels of PC [35, 36] so the total amount of choline-containing lipids was similar in rafts and plasma membranes. Such a composition of lipids present in the rafts led to a less fluid state than the surrounding membrane due to the tight packing of SM and cholesterol. 

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GPI anchoring is a posttranslational modification occurring in the endoplasmic reticulum where preassembled GPI anchor precursors are transferred to proteins bearing a C-terminal GPI signal sequence. The GPI anchor precursors are synthesized in the endoplasmic reticulum by sequential addition of sugar and other components to phosphatidylinositol. Protein GPI anchors are ubiquitous in eukaryotic cells. In mammalian cells, GPI anchored proteins are often found in lipid rafts which are subdomains of the plasma membrane, containing various signaling components. 

Lipid rafts are specific subdomains of the plasma membrane that are enriched in cholesterol and sphin-golipids many signaling molecules are apparently concentrated in these subdomains. 

Lipid Rafts Caveolae Are Special Features of Some Membranes... 

While the fluid mosaic model of membrane stmcture has stood up well to detailed scrutiny, additional features of membrane structure and function are constantly emerging. Two structures of particular current interest, located in surface membranes, are tipid rafts and caveolae. The former are dynamic areas of the exo-plasmic leaflet of the lipid bilayer enriched in cholesterol and sphingolipids they are involved in signal transduction and possibly other processes. Caveolae may derive from lipid rafts. Many if not all of them contain the protein caveolin-1, which may be involved in their formation from rafts. Caveolae are observable by electron microscopy as flask-shaped indentations of the cell membrane. Proteins detected in caveolae include various components of the signal-transduction system (eg, the insutin receptor and some G proteins), the folate receptor, and endothetial nitric oxide synthase (eNOS). Caveolae and lipid rafts are active areas of research, and ideas concerning them and their possible roles in various diseases are rapidly evolving. 

Jolly C, Sattentau QJ. Human immunodeficiency virus type 1 virological synapse formation in T cells requires lipid raft integrity. J Virol 2005 79(18) 12088-12094. 

Simons K, Toomre D. Lipid rafts and signal transduction. Nat Rev 2000 1 31-39. 

Subczynski, W. K., J. Widomska, A. Wisniewska, and A. Kusumi. 2007a. Saturation-recovery electron paramagnetic resonance discrimination by oxygen transport (DOT) method for characterizing membrane domains. In Methods in Molecular Biology Lipid Rafts, ed. T. J. McIntosh, Vol. 398, pp. 145-159, Totowa, NJ Humana Press. 

Fig. 3.11. FRET FLIM experiment to study colocalization of two lipid raft markers, GPI-GFP and CTB-Alexa594. The rows of images show intensity and lifetime images of donor-labeled and donor + acceptor-labeled cells. The histogram shows the lifetime distribution of the whole cells. The FRET...

The presence of the acceptor, lower row of images, results in a clear reduction in the lifetime to about 2.05 ns. The reduction corresponds to a 6% FRET efficiency. Experiments on more cells (.N = 4, not shown) confirms that this reduction is indeed significant and that the two lipid raft markers colocalize in the plasma membrane. 

Santuccione, A., Sytnyk, V., Leshchyns ka, I., and Schachner, M. (2005) Prion protein recruits its neuronal receptor NCAM to lipid rafts to activate p59fyn and to enhance neurite outgrowth. J. Cell Biol. 169, 341-354. 

Much of the plasma membrane cholesterol is removed by incubating cells with P-methylcyclodextrin for several hours. Cells remain viable after this treatment but the raft fraction is reduced and it is inferred that the depleted proteins are normally associated with cholesterol-dependent lipid rafts. Some, but not all, glycosylphosphatidylinositol (GPI)-anchored proteins are recovered in the fractions defined by this procedure. 

Munro, S. Lipid rafts elusive or illusive Cell 115 377-388, 2003. 

Foster, L. J., de Hoog, C. L. and Mann, M. Unbiased quantitative proteomics of lipid rafts reveals high specificity for signaling factors. Proc. Natl. Acad. Sci. U.S.A. 100 5813— 5818,2003. 

Parton, R. G. and Hancock, J. F. Lipid rafts and plasma membrane microorganization insights from Ras. Trends Cell Biol. 14 141-147, 2004. 

A major scaffolding protein of the PSD is PSD95. Two N-terminal cysteines of this protein bind palmitic acid residues, which anchor PSD95 to lipid rafts [30], PSD95 contains several domains that bind other proteins three so-called PDZ domains (short for PSD95/disc large/zona occludens-1), a src homology (SH3) domain, and a gua-nylate kinase (GK) domain. This family of proteins are... 

Hering, H., Lin, C. C. and Sheng, M. Lipid rafts in the maintenance of synapses, dendritic spines, and surface AMPA receptor stability. /. Neurosci. 23 3262-3271, 2003. 

Pseudo-glycolipids. The interest for glycolipids is connected with their occurrence in biological systems, as well as their physicochemical properties, the two viewpoints being sometimes correlated. For example in membranes, lipid rafts are sub-domains which contain liquid-ordered phases.73... 

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