Lipid rafts protein

Borner et al. (2005) took a different approach to address the specific localization of DRM proteins to lipid rafts. In this smdy the relative enrichment of proteins in the detergent-resistant fraction versus total cell membranes was used as a measure of the specificity of putative lipid raft proteins. In their study Bomer et al. used Arabidopsis thaliana as the model system so a direct comparison with mammalian DRM reports is difficult and perhaps unfair since it is not always clear what the human homologue of a plant protein is. However, it is interesting to note that Bomer et al. also found that the common contaminants in DRMs are certain highly abundant mitochondrial and endoplasmic reticulum proteins. 

Li, N., Shaw, A.R., Zhang, N.,Mak,A. andLi, L.(2004)Lipidraftproteomics analysis of in-solution digest of sodium dodecyl sulfate-solubilized lipid raft proteins by liquid chromatography-matrix-assisted laser desorption/ionization tandem mass spectrometry. Proteomics 4, 3156-3166. 

The expression of a lipid raft protein (MAT) has been detected in approximately 50% of cases and is thought to be quite specific for this lymphoma. MAT expression is typically not seen in other diffuse large B-cell lymphomas. MAT expression appears to be limited to a minor subpopulation of thymic medullary B cells, which lends further support for the thymic B-cell origin for this lymphoma. 

Zhai J, StrSm AL, Kilty R, Venkatakrishnan P, White J, Everson WV, Smart EJ, Zhu H (2009) Proteomic characterization of lipid raft proteins in amyotrophic lateral sclerosis mouse spinal cord. FEBS J 276 3308-3323... 

Parkin ET, Turner AJ, Hooper NM. Amyloid precursor protein, although partially detergent-insoluble in mouse cerebral cortex, behaves as an at)fpical lipid raft protein. Biochem J. 1999 344(Pt l) 23-30. 

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. 

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. 

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. 

The structure and roles of membrane microdomains (rafts) in cell membranes are under intensive study but many aspects are still unresolved. Unlike in synthetic bilayers (Fig. 2-2), no way has been found to directly visualize rafts in biomembranes [22]. Many investigators operationally define raft components as those membrane lipids and proteins (a) that remain insoluble after extraction with cold 1% Triton X-100 detergent, (b) that are recovered as a low density band that can be isolated by flotation centrifugation and (c) whose presence in this fraction should be reduced by cholesterol depletion. 

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. 

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... 

P. Oh and J. E. Schnitzer. Segregation of heterotrimeric G proteins in cell surface microdomains. Gq binds caveolin to concentrate in caveolae, whereas Gi and Gs target lipid rafts by default. Mol. Biol. Cell 12 685-698 (2001). 

Y. Lavie and M. Liscovitch. Changes in lipid and protein constituents of rafts and caveolae in multidrug resistant cancer cells and their functional consequences. Glycoconj. J. 17 253-259 (2000). 

J. Wang, W. Gunning, K. M. Kelley, and M. Ratnam. Evidence for segregation of heterologous GPI-anchored proteins into separate lipid rafts within the plasma membrane. J. Membr. Biol. 189 35—43 (2002). 

Fittipaldi A, Ferrari A, Zoppe M, et al. Cell membrane lipid rafts mediate caveolar endocytosis of HIV-1 Tat fusion proteins. J Biol Chem 2003 278(36) 34141-34149. 

It should be noted that the protein caveolin-1 is not necessarily an integral part of caveolae. The so-called lipid-raft mediated pathways have been studied mainly in cells that do not express caveolin-1. Apparently, these mechanisms are similar to caveolae uptake and are therefore discussed in the caveolae section. For detailed reviews on caveolae uptake, see Refs. (25-30). 

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