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Journal of Lipid Research, Vol. 44, 655-667, April 2003
Copyright © 2003 by Lipid Research, Inc.

Thematic Review

Lipid rafts

Linda J. Pike¹

Washington University School of Medicine, Department of Biochemistry and Molecular Biophysics, 660 So. Euclid, Box 8231, St. Louis, MO 63110

¹ To whom correspondence should be addressed. e-mail: 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 nonionic 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 nonspecific 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.

Abbreviations: EGF, epidermal growth factor; GPI, glycosylphosphatidylinositol; NGF, nerve growth factor; PDGF, platelet-derived growth factor; PtdIns(4,5)P₂, phosphatidylinositol 4,5-bisphosphate

Supplementary key words cholesterol • signal transduction • liquid-ordered domains

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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]

				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]

				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]

				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]

				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]

				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]

				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]

				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]

				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]

				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]

				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]

				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]

				C. B. Baron and R. F. Coburn Smooth muscle raft-like membranes J. Lipid Res., January 1, 2004; 45(1): 41 - 53. [Abstract] [Full Text] [PDF]

				K. J. McQuade and A. C. Rapraeger Syndecan-1 Transmembrane and Extracellular Domains Have Unique and Distinct Roles in Cell Spreading J. Biol. Chem., November 21, 2003; 278(47): 46607 - 46615. [Abstract] [Full Text] [PDF]

				Y. Chen, N. Takizawa, J. L. Crowley, S. W. Oh, C. L. Gatto, T. Kambara, O. Sato, X.-d. Li, M. Ikebe, and E. J. Luna F-actin and Myosin II Binding Domains in Supervillin J. Biol. Chem., November 14, 2003; 278(46): 46094 - 46106. [Abstract] [Full Text] [PDF]

				L. Liu, A. E. Bortnick, M. Nickel, P. Dhanasekaran, P. V. Subbaiah, S. Lund-Katz, G. H. Rothblat, and M. C. Phillips Effects of Apolipoprotein A-I on ATP-binding Cassette Transporter A1-mediated Efflux of Macrophage Phospholipid and Cholesterol: FORMATION OF NASCENT HIGH DENSITY LIPOPROTEIN PARTICLES J. Biol. Chem., October 31, 2003; 278(44): 42976 - 42984. [Abstract] [Full Text] [PDF]

				D. Hoekstra, O. Maier, J. M. van der Wouden, T. A. Slimane, and S. C. D. van IJzendoorn Membrane dynamics and cell polarity: the role of sphingolipids J. Lipid Res., May 1, 2003; 44(5): 869 - 877. [Abstract] [Full Text] [PDF]

				J. M. Dietschy and S. D. Turley Thematic review series: Brain Lipids. Cholesterol metabolism in the central nervous system during early development and in the mature animal J. Lipid Res., August 1, 2004; 45(8): 1375 - 1397. [Abstract] [Full Text] [PDF]