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Papers In Press, published online ahead of print February 1, 2003
J. Lipid Res., doi:10.1194/jlr.R200021-JLR200
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Biochemistry and Molecular Biophysics, Washington University School of Medicine, St. Louis, MO 63110
Corresponding Author: pike{at}biochem.wustl.edu
Lipid rafts are subdomains of the plasma membrane that contain high concentrations of cholesterol and glycosphingolipids. They exist as distinct liquid-ordered regions of the membrane that are resistant to extraction with non-ionic detergents. Rafts appear to be small in size but may constitute a relatively large fraction of the plasma membrane. While rafts have a distinctive protein and lipid composition, all rafts do not appear to be identical in terms of either the proteins or the lipids that they contain. A variety of proteins, especially those involved in cell signaling, have been shown to partition into lipid rafts. As a result, lipid rafts are thought to be involved in the regulation of signal transduction. Experimental evidence suggests that there are probably several different mechanisms through which rafts control cell signaling. For example, rafts may contain incomplete signaling pathways that are activated when a receptor or other required molecule is recruited into the raft. Rafts may also be important in limiting signaling, either by physical sequestration of signaling components to block non-specific interactions or by suppressing the intrinsic activity of signaling proteins present within rafts. This review provides an overview of the physical characteristics of lipid rafts and summarizes studies that have helped to elucidate the role of lipid rafts in signaling via receptor tyrosine kinases and G protein-coupled receptors.
Revised on January 16, 2003
Accepted on January 27, 2003
Lipid Rafts: Bringing Order to Chaos
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K. Gaus, M. Rodriguez, K. R. Ruberu, I. Gelissen, T. M. Sloane, L. Kritharides, and W. Jessup Domain-specific lipid distribution in macrophage plasma membranes J. Lipid Res., July 1, 2005; 46(7): 1526 - 1538. [Abstract] [Full Text] [PDF]
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H. Shogomori, A. T. Hammond, A. G. Ostermeyer-Fay, D. J. Barr, G. W. Feigenson, E. London, and D. A. Brown Palmitoylation and Intracellular Domain Interactions Both Contribute to Raft Targeting of Linker for Activation of T Cells J. Biol. Chem., May 13, 2005; 280(19): 18931 - 18942. [Abstract] [Full Text] [PDF]
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J. L. Macdonald and L. J. Pike A simplified method for the preparation of detergent-free lipid rafts J. Lipid Res., May 1, 2005; 46(5): 1061 - 1067. [Abstract] [Full Text] [PDF]
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J. Reyes-del Valle, S. Chavez-Salinas, F. Medina, and R. M. del Angel Heat Shock Protein 90 and Heat Shock Protein 70 Are Components of Dengue Virus Receptor Complex in Human Cells J. Virol., April 15, 2005; 79(8): 4557 - 4567. [Abstract] [Full Text] [PDF]
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J. Wharton, T. Meshulamy, G. Vallega, and P. Pilch Dissociation of Insulin Receptor Expression and Signaling from Caveolin-1 Expression J. Biol. Chem., April 8, 2005; 280(14): 13483 - 13486. [Abstract] [Full Text] [PDF]
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 R. E. Martin, M. H. Elliott, R. S. Brush, and R. E. Anderson Detailed Characterization of the Lipid Composition of Detergent-Resistant Membranes from Photoreceptor Rod Outer Segment Membranes Invest. Ophthalmol. Vis. Sci., April 1, 2005; 46(4): 1147 - 1154. [Abstract] [Full Text] [PDF]
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M. Bari, N. Battista, F. Fezza, A. Finazzi-Agro, and M. Maccarrone Lipid Rafts Control Signaling of Type-1 Cannabinoid Receptors in Neuronal Cells: IMPLICATIONS FOR ANANDAMIDE-INDUCED APOPTOSIS J. Biol. Chem., April 1, 2005; 280(13): 12212 - 12220. [Abstract] [Full Text] [PDF]
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 O. Barreiro, M. Yanez-Mo, M. Sala-Valdes, M. D. Gutierrez-Lopez, S. Ovalle, A. Higginbottom, P. N. Monk, C. Cabanas, and F. Sanchez-Madrid Endothelial tetraspanin microdomains regulate leukocyte firm adhesion during extravasation Blood, April 1, 2005; 105(7): 2852 - 2861. [Abstract] [Full Text] [PDF]
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J. Tsui, M. Inagaki, and H. Schulman Calcium/Calmodulin-dependent Protein Kinase II (CaMKII) Localization Acts in Concert with Substrate Targeting to Create Spatial Restriction for Phosphorylation J. Biol. Chem., March 11, 2005; 280(10): 9210 - 9216. [Abstract] [Full Text] [PDF]
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 E. L. Riddle, R. A. Schwartzman, M. Bond, and P. A. Insel Multi-Tasking RGS Proteins in the Heart: The Next Therapeutic Target? Circ. Res., March 4, 2005; 96(4): 401 - 411. [Abstract] [Full Text] [PDF]
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V. C. J. Fawcett and U. Lorenz Localization of Src Homology 2 Domain-Containing Phosphatase 1 (SHP-1) to Lipid Rafts in T Lymphocytes: Functional Implications and a Role for the SHP-1 Carboxyl Terminus J. Immunol., March 1, 2005; 174(5): 2849 - 2859. [Abstract] [Full Text] [PDF]
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A. J. Crossthwaite, T. Seebacher, N. Masada, A. Ciruela, K. Dufraux, J. E. Schultz, and D. M. F. Cooper The Cytosolic Domains of Ca2+-sensitive Adenylyl Cyclases Dictate Their Targeting to Plasma Membrane Lipid Rafts J. Biol. Chem., February 25, 2005; 280(8): 6380 - 6391. [Abstract] [Full Text] [PDF]
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D. V. Laurents, P. M. Gorman, M. Guo, M. Rico, A. Chakrabartty, and M. Bruix Alzheimer's A{beta}40 Studied by NMR at Low pH Reveals That Sodium 4,4-Dimethyl-4-silapentane-1-sulfonate (DSS) Binds and Promotes {beta}-Ball Oligomerization J. Biol. Chem., February 4, 2005; 280(5): 3675 - 3685. [Abstract] [Full Text] [PDF]
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 T. Tang, M. Kmet, L. Corral, S. Vartanian, A. Tobler, and J. Papkoff Testisin, a Glycosyl-Phosphatidylinositol-Linked Serine Protease, Promotes Malignant Transformation In vitro and In vivo Cancer Res., February 1, 2005; 65(3): 868 - 878. [Abstract] [Full Text] [PDF]
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K. G. Harikumar, V. Puri, R. D. Singh, K. Hanada, R. E. Pagano, and L. J. Miller Differential Effects of Modification of Membrane Cholesterol and Sphingolipids on the Conformation, Function, and Trafficking of the G Protein-coupled Cholecystokinin Receptor J. Biol. Chem., January 21, 2005; 280(3): 2176 - 2185. [Abstract] [Full Text] [PDF]
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N. Garmy, N. Taieb, N. Yahi, and J. Fantini Interaction of cholesterol with sphingosine: physicochemical characterization and impact on intestinal absorption J. Lipid Res., January 1, 2005; 46(1): 36 - 45. [Abstract] [Full Text] [PDF]
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J. Goral and E. J. Kovacs In Vivo Ethanol Exposure Down-Regulates TLR2-, TLR4-, and TLR9-Mediated Macrophage Inflammatory Response by Limiting p38 and ERK1/2 Activation J. Immunol., January 1, 2005; 174(1): 456 - 463. [Abstract] [Full Text] [PDF]
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 S. Suzuki, T. Numakawa, K. Shimazu, H. Koshimizu, T. Hara, H. Hatanaka, L. Mei, B. Lu, and M. Kojima BDNF-induced recruitment of TrkB receptor into neuronal lipid rafts: roles in synaptic modulation J. Cell Biol., December 20, 2004; 167(6): 1205 - 1215. [Abstract] [Full Text] [PDF]
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 S. M. Bared, C. Buechler, A. Boettcher, R. Dayoub, A. Sigruener, M. Grandl, C. Rudolph, A. Dada, and G. Schmitz Association of ABCA1 with Syntaxin 13 and Flotillin-1 and Enhanced Phagocytosis in Tangier Cells Mol. Biol. Cell, December 1, 2004; 15(12): 5399 - 5407. [Abstract] [Full Text] [PDF]
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L. Cezanne, S. Lecat, B. Lagane, C. Millot, J.-Y. Vollmer, H. Matthes, J.-L. Galzi, and A. Lopez Dynamic Confinement of NK2 Receptors in the Plasma Membrane: IMPROVED FRAP ANALYSIS AND BIOLOGICAL RELEVANCE J. Biol. Chem., October 22, 2004; 279(43): 45057 - 45067. [Abstract] [Full Text] [PDF]
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M. Xue, C. M. Vines, T. Buranda, D. F. Cimino, T. A. Bennett, and E. R. Prossnitz N-Formyl Peptide Receptors Cluster in an Active Raft-associated State Prior to Phosphorylation J. Biol. Chem., October 22, 2004; 279(43): 45175 - 45184. [Abstract] [Full Text] [PDF]
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A. J. Davis, I. Y. Perera, and W. F. Boss Cyclodextrins enhance recombinant phosphatidylinositol phosphate kinase activity J. Lipid Res., September 1, 2004; 45(9): 1783 - 1789. [Abstract] [Full Text] [PDF]
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K. Hueffer, L. M. Palermo, and C. R. Parrish Parvovirus Infection of Cells by Using Variants of the Feline Transferrin Receptor Altering Clathrin-Mediated Endocytosis, Membrane Domain Localization, and Capsid-Binding Domains J. Virol., June 1, 2004; 78(11): 5601 - 5611. [Abstract] [Full Text] [PDF]
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R. S. Ostrom, R. A. Bundey, and P. A. Insel Nitric Oxide Inhibition of Adenylyl Cyclase Type 6 Activity Is Dependent upon Lipid Rafts and Caveolin Signaling Complexes J. Biol. Chem., May 7, 2004; 279(19): 19846 - 19853. [Abstract] [Full Text] [PDF]
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Y. El Fakhry, M. Bouillon, C. Leveille, A. Brunet, H. Khalil, J. Thibodeau, and W. Mourad Delineation of the HLA-DR Region and the Residues Involved in the Association with the Cytoskeleton J. Biol. Chem., April 30, 2004; 279(18): 18472 - 18480. [Abstract] [Full Text] [PDF]
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A. L. Kindzelskii, R. G. Sitrin, and H. R. Petty Cutting Edge: Optical Microspectrophotometry Supports the Existence of Gel Phase Lipid Rafts at the Lamellipodium of Neutrophils: Apparent Role in Calcium Signaling J. Immunol., April 15, 2004; 172(8): 4681 - 4685. [Abstract] [Full Text] [PDF]
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 M. J. Costa, Y. Song, P. Macours, C. Massart, M. C. Many, S. Costagliola, J. E. Dumont, J. Van Sande, and V. Vanvooren Sphingolipid-Cholesterol Domains (Lipid Rafts) in Normal Human and Dog Thyroid Follicular Cells Are Not Involved in Thyrotropin Receptor Signaling Endocrinology, March 1, 2004; 145(3): 1464 - 1472. [Abstract] [Full Text] [PDF]
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L. Boyer, S. Travaglione, L. Falzano, N. C. Gauthier, M. R. Popoff, E. Lemichez, C. Fiorentini, and A. Fabbri Rac GTPase Instructs Nuclear Factor-{kappa}B Activation by Conveying the SCF Complex and IkB{alpha} to the Ruffling Membranes Mol. Biol. Cell, March 1, 2004; 15(3): 1124 - 1133. [Abstract] [Full Text] [PDF]
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R. K. Keller, T. P. Arnold, and S. J. Fliesler Formation of 7-dehydrocholesterol-containing membrane rafts in vitro and in vivo, with relevance to the Smith-Lemli-Opitz syndrome J. Lipid Res., February 1, 2004; 45(2): 347 - 355. [Abstract] [Full Text] [PDF]
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J. Kim, R. M. Adam, K. R. Solomon, and M. R. Freeman Involvement of Cholesterol-Rich Lipid Rafts in Interleukin-6-Induced Neuroendocrine Differentiation of LNCaP Prostate Cancer Cells Endocrinology, February 1, 2004; 145(2): 613 - 619. [Abstract] [Full Text] [PDF]
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H. Zhang, P. H. Links, J. K. Ngsee, K. Tran, Z. Cui, K. W. S. Ko, and Z. Yao Localization of Low Density Lipoprotein Receptor-related Protein 1 to Caveolae in 3T3-L1 Adipocytes in Response to Insulin Treatment J. Biol. Chem., January 16, 2004; 279(3): 2221 - 2230. [Abstract] [Full Text] [PDF]
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