Lipid Rafts

Abstract

The knowledge about the structure of the biological membrane changed during the last 70 years. In the 70s, Singer and Nicholson proposed the fluid mosaic model, a major conceptual breakthrough in which amphiphilic proteins reside within the lipid bilayer. In this dynamic structure, components can move laterally. Further works led to major modifications of this model. Indeed, functional aspects of trafficking and signal transduction suggested that lipids and proteins do not distribute randomly but can be sequestered in small domains, thus enhancing protein–protein interactions and speeding up signal transduction and enzyme activity. The ‘raft hypothesis’ was born. Rafts are small and transient microdomains enriched in sphingolipids and sterols, together with specific proteins with important functions. This hypothesis explains the heterogeneity of the distribution of membrane proteins by a spontaneous demixing of lipids to form domains involved in signal transduction, cell trafficking and host–pathogen relationship.

Key Concepts:

  • Biological membranes are organised in small, dynamic and transient domains called lipid rafts.

  • Lipid rafts exist in all eukaryotic cells, mostly in the plasma membrane.

  • Lipid rafts are enriched in sphingolipids and sterols, and depleted in phosphoglycerolipids.

  • Lipid rafts are involved in signal transduction pathways, cell trafficking and host–pathogen relationship.

Keywords: sphingolipids; sterols; phosphoglycerolipids; signalling; domains; epithelial cells; detergent; detergent‐insoluble membranes (DIM); detergent‐resistant membranes (DRM); detergent‐soluble membranes (DSM)

Figure 1.

Animal and plant polarised cells. (a) Polarised animal intestinal epithelial cell exhibit targeting of PM proteins to the basolateral or apical membranes with tight junctions that delineate the two regions by preventing lateral diffusion. Localisation of carbonic anhydrase XII, apical localisation of carbonic anhydrase IV, and basolasteral redistribution of β(1)‐integrin or Na+/K+ ATPase after a pathogen‐induced change in cellular polarity. Dashed lines denote redistributed proteins. (b) Plant cells have cell walls and lack tight junctions to define the polarity of the cell. Four types of PM domains have been documented in plants. Nonpolar localisation of the ATPase, basal localisation of plant hormone auxin transporter PIN1, lateral localisation of GPI‐anchored protein COBRA, apical localisation of auxin transporter AUX1, and vectorial redistribution of PIN3 after a gravitropic stimulus. Reproduced from Murphy et al. with permission of Annual Reviews, Inc.

Figure 2.

Spatial organisation of membrane rafts; Ternary lipid phase diagram for a lipid mixture imitating plasma membrane. (a) Structure of main lipids found in biological membranes. Reproduced from Munro with permission from Elsevier.. (b) Spatial organisation of sterols, phosphoglycerolipids and sphingolipids in raft domains. Reproduced from Quinn with permission from Elsevier. (c) Phase diagrams at 37 °C of three‐component bilayer mixture at different concentration (egg‐phosphatidylcholine:egg‐sphingomyelin:cholesterol, that is, a high‐ and low‐melting point lipids together with sterol) showing the co‐existence of Lo and Ld phases. Around the diagram is depicted structures of lipid bilayers with G:gel phase, solid ordered; Ld: liquid disordered phase; Lo=liquid ordered phase. Reproduced from Simons K and Ikonen E (1997) Functional Rafts in Cell Membranes. Nature387(6633): 569–572.

Figure 3.

Chemical structures of some animal and plant raft lipids. Reproduced from Bodin S, Tronchere H and Payrastre B (2003) Lipid Rafts Are Critical Membrane Domains in Blood Platelet Activation Processes. Biochimica et Biophysica Acta1610: 247–257, with permission from Elsevier.

Figure 4.

Proteins found enriched in membrane raft of the plasma membrane according to their anchorage and putative coalescence of raft after stimulus. (a) Caveolin are shown in green in a caveolae, a morphologically discrete flask‐shaped structure with raft properties. Acylated proteins (orange) partition into rafts (yellow) in the inner leaflet of the PM, and in close proximity to caveolin. Glycosphingolipid‐enriched domains (pink) are shown in the outer leaflet of the PM, enriched in GPI‐anchored proteins (red). All these domains are too small to resolve by fluorescence microscopy, with the exception of caveolae. (b) Stimuli‐induced raft (in red) coalescence, which facilitates the clustering of signalling‐related molecules allowing a rapid signal transduction inside the cells.Reproduced from Kenworthy A (2002) Peering Inside Lipid Rafts and Caveolae. Trends in Biochemical Sciences27(9): 435–437, with permission from Elsevier.

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References

Allen JA, Halverson‐Tamboli RA and Rasenick MM (2007) Lipid raft microdomains and neurotransmitter signalling. Nature Reviews Neuroscience 8: 128–140.

Anderson RG and Jacobson K (2002) A role for lipid shells in targeting proteins to caveolae, rafts, and other lipid domains. Science 296: 1821–1825.

Bagnat M, Chang A and Simons K (2001) Plasma membrane proton ATPase Pma1p requires raft association for surface delivery in yeast. Molecular Biology of the Cell 12: 4129–4138.

Borner GH, Sherrier DJ, Weimar T et al. (2005) Analysis of detergent‐resistant membranes in Arabidopsis. Evidence for plasma membrane lipid rafts. Plant Physiology 137: 104–116.

Brasitus TA and Schachter D (1984) Lipid composition and fluidity of rat enterocyte basolateral membranes. Regional differences. Biochimica et Biophysica Acta 774: 138–146.

Brown DA (2006) Lipid rafts, detergent‐resistant membranes, and raft targeting signals. Physiology (Bethesda) 21: 430–439.

Brown DA and London E (1997) Structure of detergent‐resistant membrane domains: does phase separation occur in biological membranes? Biochemical and Biophysical Research Communications 240: 1–7.

Brown DA and Rose JK (1992) Sorting of GPI‐anchored proteins to glycolipid‐enriched membrane subdomains during transport to the apical cell surface. Cell 68: 533–544.

Dufourc EJ (2008) Sterols and membrane dynamics. Journal of Chemical Biology 1: 63–77.

Fridriksson EK, Shipkova PA, Sheets ED et al. (1999) Quantitative analysis of phospholipids in functionally important membrane domains from RBL‐2H3 mast cells using tandem high‐resolution mass spectrometry. Biochemistry 38: 8056–8063.

Garner AE, Smith DA and Hooper NM (2007) Sphingomyelin chain length influences the distribution of GPI‐anchored proteins in rafts in supported lipid bilayers. Molecular Membrane Biology 24: 233–242.

Haney CH, Riely BK, Tricoli DM et al. (2011) Symbiotic rhizobia bacteria trigger a change in localization and dynamics of the Medicago truncatula receptor kinase LYK3. Plant Cell 23: 2774–2787.

Heerklotz H (2002) Triton promotes domain formation in lipid raft mixtures. Biophysical Journal 83: 2693–2701.

van't Hof W, Silvius J, Wieland F and van Meer G (1992) Epithelial sphingolipid sorting allows for extensive variation of the fatty acyl chain and the sphingosine backbone. Biochemical Journal 283(3): 913–917.

Jacobson K, Mouritsen OG and Anderson RG (2007) Lipid rafts: at a crossroad between cell biology and physics. Nature Cell Biology 9: 7–14.

Kamiguchi H (2006) The region‐specific activities of lipid rafts during axon growth and guidance. Journal of Neurochemistry 98: 330–335.

Kierszniowska S, Seiwert B and Schulze WX (2009) Definition of Arabidopsis sterol‐rich membrane microdomains by differential treatment with methyl‐beta‐cyclodextrin and quantitative proteomics. Molecular & Cellular Proteomics 8: 612–623.

Kusumi A, Ike H, Nakada C, Murase K and Fujiwara T (2005) Single‐molecule tracking of membrane molecules: plasma membrane compartmentalization and dynamic assembly of raft‐philic signaling molecules. Seminars in Immunology 17: 3–21.

Laloi M, Perret AM, Chatre L et al. (2007) Insights into the role of specific lipids in the formation and delivery of lipid microdomains to the plasma membrane of plant cells. Plant Physiology 143: 461–472.

Le Grimellec C, Friedlander G and Giocondi MC (1988) Asymmetry of plasma membrane lipid order in Madin‐Darby Canine Kidney cells. American Journal of Physiology 255: F22–F32.

Lefebvre B, Furt F, Hartmann MA et al. (2007) Characterization of lipid rafts from Medicago truncatula root plasma membranes: a proteomic study reveals the presence of a raft‐associated redox system. Plant Physiology 144: 402–418.

Lichtenberg D, Goni FM and Heerklotz H (2005) Detergent‐resistant membranes should not be identified with membrane rafts. Trends in Biochemical Sciences 30: 430–436.

Lisanti MP, Sargiacomo M, Graeve L, Saltiel AR and Rodriguez‐Boulan E (1988) Polarized apical distribution of glycosyl‐phosphatidylinositol‐anchored proteins in a renal epithelial cell line. Proceedings of the National Academy of Sciences of the USA 85: 9557–9561.

Macdonald JL and Pike LJ (2005) A simplified method for the preparation of detergent‐free lipid rafts. Journal of Lipid Research 46: 1061–1067.

Marguet D, Lenne PF, Rigneault H and He HT (2006) Dynamics in the plasma membrane: how to combine fluidity and order. EMBO Journal 25: 3446–3457.

Maxfield FR and Wustner D (2002) Intracellular cholesterol transport. Journal of Clinical Investigation 110: 891–898.

van Meer G and Simons K (1982) Viruses budding from either the apical or the basolateral plasma membrane domain of MDCK cells have unique phospholipid compositions. EMBO Journal 1: 847–852.

van Meer G, Gumbiner B and Simons K (1986) The tight junction does not allow lipid molecules to diffuse from one epithelial cell to the next. Nature 322: 639–641.

van Meer G, Stelzer EH, Wijnaendts‐van‐Resandt RW and Simons K (1987) Sorting of sphingolipids in epithelial (Madin‐Darby canine kidney) cells. Journal of Cell Biology 105: 1623–1635.

Meiri KF (2005) Lipid rafts and regulation of the cytoskeleton during T cell activation. Philosophical Transactions of the Royal Society of London. Series B, Biological Sciences 360: 1663–1672.

Melkonian KA, Ostermeyer AG, Chen JZ, Roth MG and Brown DA (1999) Role of lipid modifications in targeting proteins to detergent‐resistant membrane rafts. Many raft proteins are acylated, while few are prenylated. Journal of Biological Chemistry 274: 3910–3917.

de Meyer F and Smit B (2009) Effect of cholesterol on the structure of a phospholipid bilayer. Proceedings of the National Academy of Sciences of the USA 106: 3654–3658.

Molitoris BA and Simon FR (1986) Maintenance of epithelial surface membrane lipid polarity: a role for differing phospholipid translocation rates. Journal of Membrane Biology 94: 47–53.

Mongrand S, Morel J, Laroche J et al. (2004) Lipid rafts in higher plant cells: purification and characterization of Triton X‐100‐insoluble microdomains from tobacco plasma membrane. Journal of Biological Chemistry 279: 36277–36286.

Morel J, Claverol S, Mongrand S et al. (2006) Proteomics of plant detergent‐resistant membranes. Molecular & Cellular Proteomics 5: 1396–1411.

Morrow IC and Parton RG (2005) Flotillins and the PHB domain protein family: rafts, worms and anaesthetics. Traffic 6: 725–740.

Munro S (2003) Lipid rafts: Elusive or Illusive? Cell 115: 377–388.

Murase K, Fujiwara T, Umemura Y et al. (2004) Ultrafine membrane compartments for molecular diffusion as revealed by single molecule techniques. Biophysical Journal 86: 4075–4093.

Murphy AS, Bandyopadhyay A, Holstein SE and Peer WA (2005) Endocytotic cycling of PM proteins. Annual Review of Plant Biology 56: 221–251.

Nebl T, Pestonjamasp KN, Leszyk JD et al. (2002) Proteomic analysis of a detergent‐resistant membrane skeleton from neutrophil plasma membranes. Journal of Biological Chemistry 277: 43399–43409.

Peskan T, Westermann M and Oelmuller R (2000) Identification of low‐density Triton X‐100‐insoluble plasma membrane microdomains in higher plants. European Journal of Biochemistry 267: 6989–6995.

Pike LJ (2006) Rafts defined: a report on the Keystone Symposium on Lipid Rafts and Cell Function. Journal of Lipid Research 47: 1597–1598.

Pike LJ, Han X and Gross RW (2005) Epidermal growth factor receptors are localized to lipid rafts that contain a balance of inner and outer leaflet lipids: a shotgun lipidomics study. Journal of Biological Chemistry 280: 26796–26804.

Quinn PJ (2010) A lipid matrix model of membrane raft structure. Progress in Lipid Research 49: 390–406.

Raffaele S, Bayer E, Lafarge D et al. (2009) Remorin, a solanaceae protein resident in membrane rafts and plasmodesmata, impairs potato virus X movement. Plant Cell 21: 1541–1555.

Riethmuller J, Riehle A, Grassme H and Gulbins E (2006) Membrane rafts in host‐pathogen interactions. Biochimica et Biophysica Acta 1758: 2139–2147.

Schroeder RJ, Ahmed SN, Zhu Y, London E and Brown DA (1998) Cholesterol and sphingolipid enhance the Triton X‐100 insolubility of glycosylphosphatidylinositol‐anchored proteins by promoting the formation of detergent‐insoluble ordered membrane domains. Journal of Biological Chemistry 273: 1150–1157.

Schuck S and Simons K (2004) Polarized sorting in epithelial cells: raft clustering and the biogenesis of the apical membrane. Journal of Cell Science 117: 5955–5964.

Schuck S, Honsho M, Ekroos K, Shevchenko A and Simons K (2003) Resistance of cell membranes to different detergents. Proceedings of the National Academy of Sciences of the USA 100: 5795–5800.

Silvius JR, Read BD and McElhaney RN (1979) Thermotropic phase transitions of phosphatidylcholines with odd‐numbered n‐acyl chains. Biochimica et Biophysica Acta 555: 175–178.

Simon‐Plas F, Perraki A, Bayer E, Gerbeau‐Pissot P and Mongrand S (2011) An update on plant membrane rafts. Current Opinion in Plant Biology 14: 642–649.

Sperling P, Franke S, Luthje S and Heinz E (2005) Are glucocerebrosides the predominant sphingolipids in plant plasma membranes? Plant Physiology and Biochemistry 43: 1031–1038.

Wieser S, Moertelmaier M, Fuertbauer E, Stockinger H and Schutz GJ (2007) (Un)confined diffusion of CD59 in the plasma membrane determined by high‐resolution single molecule microscopy. Biophysical Journal 92: 3719–3728.

Xu X and London E (2000) The effect of sterol structure on membrane lipid domains reveals how cholesterol can induce lipid domain formation. Biochemistry 39: 843–849.

Zidovetzki R and Levitan I (2007) Use of cyclodextrins to manipulate plasma membrane cholesterol content: evidence, misconceptions and control strategies. Biochimica et Biophysica Acta 1768: 1311–1324.

Further Reading

Binder WH, Barragan V and Menger FM (2003) Domains and rafts in lipid membranes. Angewandte Chemie International Edition (England) 42: 5802–5827.

Furt F, Lefebvre B, Cullimore J, Bessoule JJ and Mongrand S (2007) Plant lipid rafts: fluctuat nec mergitur. Plant Signaling & Behavior 2: 508–511.

Furt F, Simon‐Plas F and Mongrand S (2011) Lipids of the plasma membrane. In: Murphy AS, Wendy P and Schulz B (eds) The Plant Plasma Membrane. Plant Cell Monographs 19, pp. 3–30. Heidelberg: Springer‐Verlag.

Grecco HE, Schmick M and Bastiaens PI (2011) Signaling from the living plasma membrane. Cell 144: 897–909.

Mongrand S, Stanislas T, Bayer EM, Lherminier J and Simon‐Plas F (2010) Membrane rafts in plant cells. Trends in Plant Science 15: 656–663.

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Germain, Véronique, Perraki, Artemis, and Mongrand, Sébastien(Sep 2012) Lipid Rafts. In: eLS. John Wiley & Sons Ltd, Chichester. http://www.els.net [doi: 10.1002/9780470015902.a0023727]