Summary
The plasma membrane is not a uniform two-dimensional space but includes various types of specialized regions containing specific lipids and proteins. These include clathrin-coated pits and caveolae. The existence of other cholesterol- and glycosphingolipid-rich microdomains has also been proposed. The aim of this review is to illustrate that these latter domains, also called lipid rafts, may be the preferential interaction sites between a variety of toxins, bacteria, and viruses and the target cell. These pathogens and toxins have hijacked components that are preferentially found in rafts, such as glycosylphosphatidylinositol-anchored proteins, sphingomyelin, and cholesterol. These molecules not only allow binding of the pathogen or toxin to the proper target cell but also appear to potentiate the toxic action. We briefly review the structure and proposed functions of cholesterol- and glycosphingolipid-rich microdomains and then describe the toxins and pathogens that interact with them. When possible the advantage conferred by the interaction with microdomains will be discussed.
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Abbreviations
- GPI:
-
glycosylphosphatidylinositol
References
Abrami L, van der Goot FG (1999) Cholesterol-sphingolipid rich plasma membrane microdomains act as concentration platforms to facilitate intoxication by aerolysin. J Cell Biol 147: 175–184
—, Fivaz M, Glauser P-E, Parton RG, van der Goot FG (1998) A pore-forming toxin interacts with a GPI-anchored protein and causes vacuolation of the endoplasmic reticulum. J Cell Biol 140: 525–540
Arni S, Ilangumaran S, Van E, Deckert G, Sandhoff K, Poincelet M, Briol A, Rungger BE, Hoessli DC (1996) Differential regulation of Src-family protein tyrosine kinases in GPI domains of T lymphocyte plasma membranes. Biochem Biophys Res Commun 225: 801–807
Baorto DM, Gao Z, Malaviya R, Dustin ML, van der Merwe A, Lublin DM, Abraham SN (1997) Survival of FimH-expressing enterobacteria in macrophages relies on glycolipid traffic. Nature 389: 636–639
Bernet-Camard MF, Coconnier MH, Hudault S, Servin AL (1996) Pathogenicity of the diffusely adhering strainEscherichia coli C1845: F1845 adhesin-decay accelerating factor interaction, brush border microvillus injury, and actin disassembly in cultured human intestinal epithelial cells. Infect Immun 64: 1918–1928
Bhakdi S, Bayley H, Valeva A, Walev I, Walker B, Kehoe M, Palmer M (1996) Staphylococcal alpha-toxin, streptolysin-O, andEscherichia coli hemolysin: prototypes of pore-forming bacterial cytolysins. Arch Microbiol 165: 73–79
Brown DA, London E (1998) Functions of lipid rafts in biological membranes. Annu Rev Cell Dev Biol 14: 111–136
Brown RE (1998) Sphingolipid organization: what physical studies of model membranes reveal. J Cell Sci 111: 1–9
Collier RJ (1990) Diphtheria toxin: structure and function of a cytocidal protein. In: Vaughan JMAM (ed) ADP-ribosylating toxins and G proteins: insights into signal transduction. American Society of Microbiology, Washington, DC, pp 3–19
Cossart P (1997) Host/pathogen interactions: subversion of the mammalian cell cytoskeleton by invasive bacteria. J Clin Invest 99: 2307–2311
Dehio C, Prevost MC, Sansonetti PJ (1995) Invasion of epithelial cells byShigella flexneri induces tyrosine phosphorylation of cortactin by a pp60c-src-mediated signalling pathway. EMBO J 14: 2471–2482
Diep DB, Nelson KL, Raja SM, McMaster RW, Buckley JT (1998) Glycosylphosphatidylinositol anchors of membrane glycoproteins are binding determinants for the channel-forming toxin Aerolysin. J Biol Chem 273: 2355–2360
Dumenil G, Olivo JC, Pellegrini S, Fellous M, Sansonetti PJ, Nhieu GT (1998) Interferon alpha inhibits a Src-mediated pathway necessary for Shigella-induced cytoskeletal rearrangements in epithelial cells. J Cell Biol 143: 1003–1012
Edidin M (1997) Lipid microdomains in cell surface membranes. Curr Opin Struct Biol 7: 528–532
Field KA, Holowka D, Baird B (1995) Fc epsilon RI-mediated recruitment of p53/561yn to detergent-resistant membrane domains accompanies cellular signaling. Proc Natl Acad Sci USA 92: 9201–9205
— — — (1997) Compartmentalized activation of the high affinity immunoglobulin E receptor within membrane domains. J Biol Chem 272: 4276–4280
Finlay BB, Cossart P (1997) Exploitation of mammalian host cell functions by bacterial pathogens. Science 276: 718–725
Friedrichson T, Kurzchalia TV (1998) Microdomains of GPI-anchored proteins in living cells revealed by crosslinking. Nature 394: 802–805
Galan JE, Pace J, Hayman MJ (1992) Involvement of the epidermal growth factor receptor in the invasion of cultured mammalian cells bySalmonella typhimurium. Nature 357: 588–589
Grimminger F, Rose F, Sibelius U, Meinhardt M, Potzsch B, Spriestersbach R, Bhakdi S, Suttorp N, Seeger W (1997) Human endothelial cell activation and mediator release in response to the bacterial exotoxinsEscherichia coli hemolysin and staphylococcal alpha-toxin. J Immunol 159: 1909–1916
Harder T, Simons K (1997) Caveolae, DIGs, and the dynamics of sphingolipid-cholesterol microdomains. Curr Opin Cell Biol 9: 534–542
—, Scheiffele P, Verkade P, Simons K (1998) Lipid domain structure of the plasma membrane revealed by patching of membrane components. J Cell Biol 141: 929–942
Harris JR, Adrian M, Bhakdi S, Palmer M (1998) Cholesterol-streptolysin O interaction: an EM study of wild-type and mutant streptolysin O. J Struct Biol 121: 343–355
Hooper NM (1998) Membrane biology: do glycolipid microdomains really exist? Curr Biol 8: R114–116
Hua G, Tsukamoto K, Rasilo ML, Ikezawa H (1998) Molecular cloning of a GPI-anchored aminopeptidase N fromBombyx mori midgut: a putative receptor forBacillus thuringiensis CryIA toxin. Gene 214: 177–185
Ilangumaran S, Briol A, Hoessli DC (1998) CD44 selectively associates with active Src family protein tyrosine kinases Lck and Fyn in glycosphingolipid-rich plasma membrane domains of human peripheral blood lymphocytes. Blood 91: 3901–3908
—, Arni S, van Echten-Deckert G, Borisch B, Hoessli DC (1999) Microdomain-dependent regulation of Lck and Fyn protein tyrosine kinases in T lymphocyte plasma membranes. Mol Biol Cell 10: 891–905
Jacobs T, Darji A, Frahm N, Rohde M, Wehland J, Chakraborty T, Weiss S (1998) Listeriolysin O: cholesterol inhibits cytolysis but not binding to cellular membranes. Mol Microbiol 28: 1081–1089
Jacobson K, Dietrich C (1999) Looking at lipid rafts? Trends Cell Biol 9: 87–91
Kitchens RL, Wang P, Munford RS (1998) Bacterial lipopolysaccharide can enter monocytes via two CD14-dependent pathways. J Immunol 161: 5534–5545
Krause K-H, Fivaz M, Monod A, van der Goot F (1998) Aerolysin induces G-protein activation and Ca2+ release from intracellular stores in human granulocytes. J Biol Chem 273: 18122–18129
Lange S, Nussler F, Kauschke E, Lutsch G, Cooper EL, Herrmann A (1997) Interaction of earthworm hemolysin with lipid membranes requires sphingolipids. J Biol Chem 272: 20884–20892
Liu P, Ying Y, Anderson RG (1997) Platelet-derived growth factor activates mitogen-activated protein kinase in isolated caveolae. Proc Natl Acad Sci USA 94: 13666–13670
Lorence A, Darszon A, Bravo A (1997) Aminopeptidase dependent pore formation ofBacillus thuringiensis Cry1Ac toxin onTrichoplusia ni membranes. FEBS Lett 414: 303–307
Mengaud J, Ohayon H, Gounon P, Mege RM, Cossart P (1996) Ecadherin is the receptor for internalin, a surface protein required for entry ofL. monocytogenes into epithelial cells. Cell 84: 923–932
Montecucco C, Papini E, Schiavo G (1994) Bacterial protein toxins penetrate cells via a four-step mechanism. FEBS Lett 3466: 92–98
Nelson KL, Raja SM, Buckley JT (1997) The GPI-anchored surface glycoprotein Thy-1 is a receptor for the channel-forming toxin aerolysin. J Biol Chem 272: 12170–12174
Orlandi PA, Fishman PH (1998) Filipin-dependent inhibition of cholera toxin: evidence for toxin internalization and activation through caveolae-like domains. J Cell Biol 141: 905–915
Parolini I, Sargiacomo M, Lisanti MP, Peschle C (1996) Signal transduction and glycophosphatidylinositol-linked proteins (lyn, lck, CD4, CD45, G proteins, and CD55) selectively localize in Triton-insoluble plasma membrane domains of human leukemic cell lines and normal granulocytes. Blood 87: 3783–3794
Parton RG (1994) Ultrastructural localization of gangliosides: GM1 is concentrated in caveolae. J Histochem Cytochem 42: 155–166
— (1996) Caveolae and caveolins. Curr Opin Cell Biol 8: 542–548
—, Lindsay MR (1999) Exploitation of major histocompatibility class I molecules and caveolae by Simian virus 40. Immunol Rev 168: 23–31
Peiffer I, Servin AL, Bernet-Camard MF (1998) Piracy of decayaccelerating factor (CD55) signal transduction by the diffusely adhering strainEscherichia coli C1845 promotes cytoskeletal Factin rearrangements in cultured human intestinal INT407 cells. Infect Immun 66: 4036–4042
Rajamohan F, Lee MK, Dean DH (1998)Bacillus thuringiensis insecticidal proteins: molecular mode of action. Prog Nucleic Acid Res Mol Biol 60: 1–27
Rietveld A, Simons K (1998) The differential miscibility of lipids as the basis for the formation of functional membrane rafts. Biochim Biophys Acta 1376: 467–479
Rosenshine I, Duronio V, Finlay BB (1992) Tyrosine protein kinase inhibitors block invasin-promoted bacterial uptake by epithelial cells. Infect Immun 60: 2211–2217
Rossjohn J, Feil SC, Mckinstry WJ, van der Goot FG, Buckley JT, Parker MW (1998) Aerolysin: a paradigm for membrane insertion of beta-sheet protein toxins. J Struct Biol 121: 92–100
Shaul PW, Anderson RG (1998) Role of plasmalemmal caveolae in signal transduction. Am J Physiol 275: L843–851
Sheets ED, Lee GM, Simson R, Jacobson K (1997) Transient confinement of a glycosylphosphatidylinositol-anchored protein in the plasma membrane. Biochemistry 36: 12449–12458
Sibelius U, Schulz EC, Rose F, Hattar K, Jacobs T, Weiss S, Chakraborty T, Seeger W, Grimminger F (1999) Role ofListeria monocytogenes exotoxins listeriolysin and phosphatidylinositol-specific phospholipase C in activation of human neutrophils. Infect Immun 67: 1125–1130
Simons K, Ikonen E (1997) Functional rafts in cell membranes. Nature 387: 569–572
Simons M, Keller P, De SB, Beyreuther K, Dotti CG, Simons K (1998) Cholesterol depletion inhibits the generation of beta-amyloid in hippocampal neurons. Proc Natl Acad Sci USA 95: 6460–6464
Solomon KR, Mallory MA, Finberg RW (1998) Determination of the non-ionic detergent insolubility and phosphoprotein associations of glycosylphosphatidylinositol-anchored proteins expressed on T cells. Biochem J 334: 325–333
Taraboulos A, Scott M, Semenov A, Avrahami D, Laszlo L, Prusiner SB, Avraham D (1995) Cholesterol depletion and modification of COOH-terminal targeting sequence of the prion protein inhibit formation of the scrapie isoform. J Cell Biol 129: 121–132
Tewari R, MacGregor JI, Ikeda T, Little JR, Hultgren SJ, Abraham SN (1993) Neutrophil activation by nascent FimH subunits of type 1 fimbriae purified from the periplasm ofEscherichia coli. J Biol Chem 268: 3009–3015
Tweten RK (1995) Pore-forming toxins of Gram-positive bacteria. In: Roth JA, Bolin CA, Brogden KA, Minion FC, Wannemuehler MJ (eds) Virulence mechanisms of bacterial pathogens. American Society of Microbiology, Washington, DC, pp 207–229
Ulevitch RJ, Tobias PS (1994) Recognition of endotoxin by cells leading to transmembrane signaling. Curr Opin Immunol 6: 125–130
van den Berg CW, Cinek T, Hallett MB, Horejsi V, Morgan BP (1995) Exogenous glycosyl phosphatidylinositol-anchored CD59 associates with kinases in membrane clusters on U937 cells and becomes Ca2+-signaling competent. J Cell Biol 131: 669–677
Varma R, Mayor S (1998) GPI-anchored proteins are organized in submicron domains at the cell surface. Nature 394: 798–801
Waugh MG, Lawson D, Hsuan JJ (1999) Epidermal growth factor receptor activation is localized within low-buoyant density, non-caveolar membrane domains. Biochem J 337: 591–597
Wolf AA, Jobling MG, Wimer-Mackin S, Ferguson-Maltzman M, Madara JL, Holmes RK, Lencer WI (1998) Ganglioside structure dictates signal transduction by cholera toxin and association with caveolae-like membrane domains in polarized epithelia. J Cell Biol 141: 917–927
Yamaji A, Sekizawa Y, Emoto K, Sakuraba H, Inoue K, Kobayashi H, Umeda M (1998) Lysenin, a novel sphingomyelin-specific binding protein. J Biol Chem 273: 5300–5306
Zitzer A, Zitzer O, Bhakdi S, Palmer M (1999) Oligomerization of vibrio cholerae cytolysin yields a pentameric pore and has a dual specificity for cholesterol and sphingolipids in the target membrane. J Biol Chem 274: 1375–1380
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Fivaz, M., Abrami, L. & van der Goot, F.G. Pathogens, toxins, and lipid rafts. Protoplasma 212, 8–14 (2000). https://doi.org/10.1007/BF01279342
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DOI: https://doi.org/10.1007/BF01279342