Chapter 21 : Trafficking of Cholera Toxin and Related Bacterial Enterotoxins: Pathways and Endpoints

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This chapter focuses on toxins of the cholera family as a paradigm for the opportunistic invasion of the mammalian intestine by exploitation of eukaryotic mechanisms of membrane trafficking, protein transport, and signal transduction. Cholera toxin (CT) enters epithelial cells of the human intestine after binding specific lipids on the host cell apical membrane. The mechanism of toxin entry is a near mirror image of protein biosynthesis in eukaryotic cells. CT represents one of the best-characterized virulence factors produced by pathogenic microorganisms, and its mode of action is discussed in detail. Labile toxins from that are antigenically similar to CT are classified as type I toxins. Montesano and coauthors first reported the localization of gold-labeled CT in non-clathrin-coated membrane invaginations of cultured liver cells and proposed the existence of at least two distinct pathways for internalization of surface-bound ligands. Human intestinal epithelial cells, however, express low levels of caveolin-1 and -2 and do not exhibit caveolae as assessed morphologically. In eukaryotic cells, translocation of nascent proteins into the endoplasmic reticulum (ER) occurs via the protein conducting channel Sec61, termed as the translocon. Recent studies indicate that protein translocation through the translocon and protein folding in the ER are reversible processes.

Citation: Rodighiero C, Lencer W. 2003. Trafficking of Cholera Toxin and Related Bacterial Enterotoxins: Pathways and Endpoints, p 385-402. In Hecht G (ed), Microbial Pathogenesis and the Intestinal Epithelial Cell. ASM Press, Washington, DC. doi: 10.1128/9781555817848.ch21

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Bacterial Proteins
Bacterial Virulence Factors
Shiga Toxin 1
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Image of FIGURE 1

Schematic representation of the structural organization of some AB toxins. (Top, from left) CT together with heat-labile enterotoxins type I and II (LT); Shiga toxin (ShT) together with Shiga-like toxins (ShLTs); pertussis toxin (PT). (Bottom, from left) Ricin toxin (RT), PEA, and diphtheria toxin (DT). Identical shapes indicate conserved functional domains, where receptor-binding subunits are cylinders, ADP-ribosyltransferase catalytic subunits are triangles, -glycosidase catalytic subunits are ovals, and translocation domains are cubes. The A domain of C/LT and Shiga and Shiga-like toxins can also be divided into an N-terminal domain (A1) and a C-terminal domain (A2) that anchor domain A1 to the pentameric binding component. The pair of scissors indicates a proteolysis-sensitive loop, and disulfide bonds are also represented (S-S). The ER retention sequence at the C terminus of the A2 fragment of Ctx is KDEL (represented) and RDEL for LT (omitted), while for PEA the signal is REDLK (represented).

Citation: Rodighiero C, Lencer W. 2003. Trafficking of Cholera Toxin and Related Bacterial Enterotoxins: Pathways and Endpoints, p 385-402. In Hecht G (ed), Microbial Pathogenesis and the Intestinal Epithelial Cell. ASM Press, Washington, DC. doi: 10.1128/9781555817848.ch21
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Image of FIGURE 2

Trafficking model for CT. Toxin enters the cell by binding to the apical surface of the polarized epithelium via G and association with lipid rafts (1). Toxin moves via endosomes to the Golgi network (2), where the C-terminal KDEL motif facilitates retrograde movement of the CT-GM1 complex to the ER (3). Release and translocation of the A-subunit occur in the ER and is a process mediated by PDI (4), while the B-subunit undergoes Golgi/ER recycling prior to degradation (5). Once in the cytosol, the A-subunit is transported to the basolateral membrane where the Gs/adenylate cyclase complex is located (6). ADP-ribosylation of the heterotrimeric GTPase Gsα by the toxin, produces an increase of intracellular cyclic AMP (cAMP) (7) that causes an active secretion of chloride (8).

Citation: Rodighiero C, Lencer W. 2003. Trafficking of Cholera Toxin and Related Bacterial Enterotoxins: Pathways and Endpoints, p 385-402. In Hecht G (ed), Microbial Pathogenesis and the Intestinal Epithelial Cell. ASM Press, Washington, DC. doi: 10.1128/9781555817848.ch21
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1. Aman, A. T.,, S. Fraser,, E. A. Merritt,, C. Rodighiero,, M. Kenny,, M. Ahn,, W. G. Hol,, N. A. Williams,, W. I. Lencer,, and T. R. Hirst. 2001. A mutant cholera toxin B subunit that binds GM1-ganglioside but lacks immunomodulatory or toxic activity. Proc. Natl. Acad. Sci. USA 98:85368541.
2. Badizadegan, K.,, B. L. Dickinson,, H. E. Wheeler,, R. S. Blumberg,, R. K. Holmes,, and W. I. Lencer. 2000. Heterogeneity of detergent insoluble membranes from human epithelia containing caveolin-1 and ganglioside GM1. Am. J. Physiol. 278:G895G904.
3. Bastiaens, P. I. H.,, I. V. Majoul,, P. J. Verveer,, H.-D. Söling,, and T. M. Jovin. 1996. Imaging the intracellular trafficking and state of the AB5 quaternary structure of cholera toxin. EMBO J. 15:42464253.
4. Bonifacino, J. S.,, and A. M. Weissman,. 1998. Ubiquitin and the control of protein fate in the secretory and endocytic pathways, p. 1957. In J. A. Spudich (ed.), Annual Review of Cell and Developmental Biology, vol. 14. Annual Reviews, Palo Alto, Calif.
5. Brodsky, J. L.,, and A. A. McCracken. 1999. ER protein quality control and proteasome-mediated protein degradation. Semin. Cell Dev. Biol. 10:507513.
6. Cassel, D.,, and T. Pfeuffer. 1978. Mechanism of cholera toxin action: covalent modification of the guanyl nucleotide-binding protein of the adenylate cyclase system. Proc. Natl. Acad. Sci. USA 75:26692673.
7. Chaudry, V. K.,, Y. Jinno,, D. Fitzgerald,, and I. Pastan. 1990. Pseudomonas exotoxin contains a specific sequence at the carboxyl terminus that is required for cytotoxicity. Proc. Natl. Acad. Sci. USA 87:308312.
8. Chege, N. W.,, and S. R. Pfeffer. 1990. Compartmentation of the Golgi complex: brefeldin-A distinguishes trans-Golgi cisternae from the trans-Golgi network. J. Cell Biol. 111:893899.
9. De, S. N. 1959. Enterotoxicity of bacterial-free culture-filtrate of Vibrio cholerae. Nature 183:15331534.
10. De, S. N.,, K. Bhattacharva,, and J. K. Sarkar. 1956. A study on the pathogenicity of strains of Bacterium coli from acute and chronic enteritis. J. Pathol. Bacteriol. 71:201209.
11. Donaldson, J. G.,, J. Lippincott-Schwartz,, and R. D. Klausner. 1991. Guanine nucleotides modulate the effects of brefeldin A in semipermeable cells: regulation of the association of a 110-kD peripheral membrane protein with the Golgi apparatus. J. Cell Biol. 112:579588.
12. Donta, S. T.,, S. Beristain,, and T. K. Tomicic. 1993. Inhibition of heat-labile cholera and Escherichia coli enterotoxins by brefeldin A. Infect. Immun. 61:32823286.
13. Drab, M.,, P. Verkade,, M. Elger,, M. Kasper,, M. Lohn,, B. Lauterbach,, J. Menne,, C. Lindschau,, F. Mende,, F. C. Luft,, A. Schedl,, H. Haller,, and T. V. Kurzchalia. 2001. Loss of caveolae, vascular dysfunction, and pulmonary defects in caveolin-1 gene-disrupted mice. Science 293:24492452.
14. Dutta, N. K.,, M. V. Panse,, and D. R. Kulkami. 1959. Role of cholera toxin in experimental cholera. J. Bacteriol. 78:594595.
15. Endo, Y.,, K. Mitsui,, M. Motizuki,, and K. Tsurugi. 1987. The mechanism of action of ricin and related toxic lectins on eukaryotic ribosomes. The site and the characteristics of the modification in 28S ribosomal RNA caused by the toxins. J. Biol. Chem. 262:59085912.
16. Falguieres, T.,, F. Mallard,, C. Baron,, D. Hanau,, C. Lingwood,, B. Goud,, J. Salamero,, and L. Johannes. 2001. Targeting of Shiga toxin b-subunit to retrograde transport route in association with detergent-resistant membranes. Mol. Biol. Cell 12:24532468.
17. Finkelstein, R. A.,, and J. J. LoSpalluto. 1969. Pathogenesis of experimental cholera: preparation of choleragen and choleragenoid. J. Exp. Med. 130:185202.
18. Finkelstein, R. A.,, H. T. Norris,, and N. K. Dutta. 1964. Pathogenesis of bacterial cholera in infant rabbits. J. Infect. Dis. 114:203216.
19. Freedman, R. B. 1989. Protein disulfide isomerase: multiple roles in the modification of nascent secretory proteins. Cell 57:10691072.
20. Freedman, R. B.,, T. R. Hirst,, and M. F. Tuite. 1994. Protein disulphide isomerase: building bridges in protein folding. Trends Biochem. Sci. 19:331336.
21. Friedrichson, T.,, and T. V. Kurzchalia. 1998. Microdomains of GPI-anchored proteins in living cells revealed by crosslinking. Nature 394:802805.
22. Fukuta, S.,, J. L. Magnani,, E. M. Twiddy,, R. K. Holmes,, and V. Ginsburg. 1988. Comparison of the carbohydrate-binding specificities of cholera toxin and Escherichia coli heat-labile enterotoxins LTh-I, LT-IIa, and LT-IIb. Infect. Immun. 56:17481753.
23. Gething, M. J.,, and J. Sambrook. 1992. Protein folding in the cell. Nature 355:3345.
24. Gill, D. M.,, and R. Meren. 1978. ADP-ribosylation of membrane proteins catalyzed by cholera toxin: basis of the activation of adenylate cyclase. Proc. Natl. Acad. Sci. USA 75:30503054.
25. Goins, B.,, and E. Freire. 1988. Thermal stability and intersubunit interactions of cholera toxin in solution and in association with its cell-surface receptor ganglioside GM1. Biochemistry 27:20462052.
26. Green, B. A.,, R. J. Neill,, W. T. Ruyechan,, and R. K. Holmes. 1983. Evidence that a new enterotoxin of Escherichia coli which activates adenylate cyclase in eucaryotic target cells is not plasmid mediated. Infect. Immun. 41:383390.
27. Guth, B. E. C.,, E. M. Twiddy,, L. R. Trabulsi,, and R. K. Holmes. 1986. Variation in chemical properties and antigenic determinants among type II heat-labile enterotoxins of Escherichia coli. Infect. Immun. 54:529536.
28. Gyles, C. L.,, and D. A. Barnum. 1969. A heat-labile enterotoxin form Escherichia coli enteropathogenic for pigs. J. Infect. Dis. 120:419426.
29. Hakomori, S.,, and Y. Igarashi. 1993. Gangliosides and glycosphingolipids as modulators of cell growth, adhesion, and transmembrane signaling. Adv. Lipid Res. 25:147162.
30. Harder, T.,, P. Scheiffele,, and K. Simons. 1998. Lipid domain structure of the plasma membrane revealed by patching of membrane components. J. Cell Biol. 141:929942.
31. Hazes, B.,, and R. J. Read. 1997. Accumulating evidence suggests that several AB-toxins subvert the endoplasmic reticulum-associated protein degradation pathway to enter target cells. Biochemistry 36:1105111054.
32. Henley, J. R.,, E. W. A. Krueger,, B. J. Oswald,, and M. A. McNiven. 1998. Dynamin-mediated internalization of caveolae. J. Cell Biol. 141:8599.
33. Hirst, T. R., 1995. Biogenesis of cholera and related oligomeric enterotoxins, p. 123184. In J. Moss,, M. Vaughan,, B. Iglewski,, and A. T. Tu (ed.), Bacterial Toxins and Virulence Factors in Disease, vol. 8. Marcel Dekker, Inc., New York, N.Y.
34. Holmes, R. K., 1997. Heat-labile enterotoxins (Escherichia coli ), p. 3033. In R. Rappuoli, and C. Montecucco (ed.), Guidebook to Protein Toxins and Their Use in Cell Biology. Oxford University Press, Oxford, United Kingdom.
35. Holmes, R. K.,, and E. M. Twiddy. 1983. Characterization of monoclonal antibodies that react with unique and cross-reacting determinants of cholera enterotoxin and its subunits. Infect. Immun. 42:914923.
36. Holmgren, J.,, P. Fredman,, M. Lindblad,, A. M. Svennerholm,, and L. Svennerholm. 1982. Rabbit intestinal glycoprotein receptor for Escherichia coli heat-labile enterotoxin lacking affinity for cholera toxin. Infect. Immun. 38:424433.
37. Holmgren, J.,, M. Lindblad,, P. Fredman,, L. Svennerholm,, and H. Myrvold. 1985. Comparison of receptors for cholera toxin and Escherichia coli enterotoxins in human intestine. Gastroenterology 89:2735.
38. Jobling, M. G.,, and R. K. Holmes. 1991. Analysis of structure and function of the B subunit of cholera toxin by the use of site-directed mutagenesis. Mol. Microbiol. 5:17551767.
39. Johannes, L.,, D. Tenza,, C. Antony,, and B. Goud. 1997. Retrograde transport of KDEL-bearing B-fragment of Shiga toxin. J. Biol. Chem. 272:1955419561.
40. Joseph, K. C.,, A. Stieber,, and N. K. Gonatas. 1979. Endocytosis of cholera toxin in GERL-like structures of murine neuroblastoma cells pretreated with GM1 ganglioside. J. Cell Biol. 81:543554.
41. Klappa, P.,, T. Stromer,, R. Zimmermann,, L. W. Ruddock,, and R. B. Freedman. 1998. A pancreas-specific glycosylated protein disulphide-isomerase binds to misfolded proteins and peptides with an interaction inhibited by oestrogens. Eur. J. Biochem. 254:6369.
42. Koch, R. 1884. An address on cholera and its bacillus. Br. Med. J. 2:403407.
43. Kovbasnjuk, O.,, M. Edidin,, and M. Donowitz. 2001. Role of lipid rafts in Shiga toxin 1 interaction with the apical surface of Caco-2 cells. J. Cell Sci. 114:40254031.
44. Kurzchalia, T. V.,, and R. G. Parton. 1996. And still they are moving.... dynamic properties of caveolae. FEBS Lett. 389:5254.
45. Kuziemko, G. M.,, M. Stroh,, and R. C. Stevens. 1996. Cholera toxin binding affinity and specificity for gangliosides determined by surface plasmon resonance. Biochemistry 35:63756384.
46. Lamaze, C.,, and S. L. Schmid. 1995. The emergence of clathrin-independent pinocytotic pathways. Curr. Opin. Cell Biol. 7:573580.
47. Lee, C.-M.,, P. P. Chang,, S.-C. Tsai,, R. Adamik,, S. R. Price,, B. C. Kunz,, J. Moss,, E. M. Twiddy,, and R. K. Holmes. 1991. Activation of Escherichia coli heat-labile enterotoxins by native and recombinant adenosine diphosphate-ribosylation factors, 20-kD guanine nucleotide-binding proteins. J. Clin. Invest. 87:17801786.
48. Lee, S. H.,, D. L. Hava,, M. K. Waldor,, and A. Camilli. 1999. Regulation and temporal expression patterns of Vibrio cholerae virulence genes during infection. Cell 99:625634.
49. Lencer, W. I.,, C. Constable,, S. Moe,, M. Jobling,, H. M. Webb,, S. Ruston,, J. L. Madara,, T. Hirst,, and R. Holmes. 1995. Targeting of cholera toxin and E. coli heat labile toxin in polarized epithelia: role of C-terminal KDEL. J. Cell Biol. 131:951962.
50. Lencer, W. I.,, C. Constable,, S. Moe,, P. A. Rufo,, A. Wolf,, M. G. Jobling,, S. P. Ruston,, J. L. Madara,, R. K. Holmes,, and T. R. Hirst. 1997. Proteolytic activation of cholera toxin and Escherichia coli labile toxin by entry into host epithelial cells: signal transduction by a protease-resistant toxin variant. J. Biol. Chem. 272:1556215568.
51. Lencer, W. I.,, J. B. de Almeida,, S. Moe,, J. L. Stow,, D. A. Ausiello,, and J. L. Madara. 1993. Entry of cholera toxin into polarized human intestinal epithelial cells: identification of an early brefeldin A sensitive event required for A1-peptide generation. J. Clin. Invest. 92:29412951.
52. Lencer, W. I.,, S. Moe,, P. A. Rufo,, and J. L. Madara. 1995. Transcytosis of cholera toxin subunits across model human intestinal epithelia. Proc. Natl. Acad. Sci. USA 92:1009410098.
53. Lewis, M. J.,, and H. R. B. Pelham. 1992. Ligand-induced redistribution of a human KDEL receptor from the Golgi complex to the endoplasmic reticulum. Cell 68:353364.
54. Ling, H.,, A. Boodhoo,, B. Hazes,, M. D. Cummings,, G. D. Armstrong,, J. L. Brunton,, and R. J. Read. 1998. Structure of the Shiga-like toxin I B-pentamer complexed with an analogue of its receptor Gb3. Biochemistry 37:17771788.
55. Lingwood, C. A. 1993. Verotoxins and their glycolipid receptors. Adv. Lipid Res. 25:189211.
56. Lord, J. M.,, and L. M. Roberts. 1998. Toxin entry: retrograde transport through the secretory pathway. J. Cell Biol. 140:733736.
57. MacKenzie, C. R.,, T. Hirama,, K. K. Lee,, E. Altman,, and N. M. Young. 1997. Quantitative analysis of bacterial toxin affinity and specificity for glycolipid receptors by surface plasmon resonance. J. Biol. Chem. 272:55335538.
58. Majoul, I.,, D. Ferrari,, and H. D. Soling. 1997. Reduction of protein disulfide bonds in an oxidizing environment. The disulfide bridge of cholera toxin A-subunit is reduced in the endoplasmic reticulum. FEBS Lett. 401:104108.
59. Majoul, I. V.,, P. I. H. Bastiaens,, and H.-D. Söling. 1996. Transport of an external Lys-Asp-Glu-Leu (KDEL) protein from the plasma membrane to the endoplasmic reticulum: studies with cholera toxin in Vero cells. J. Cell Biol. 133:777789.
60. Matlack, K. E.,, W. Mothes,, and T. A. Rapoport. 1998. Protein translocation: tunnel vision. Cell 92:381390.
61. Mekalanos, J. J.,, R. J. Collier,, and W. R. Romig. 1979. Enzymic activity of cholera toxin. II. Relationships to proteolytic processing, disulfide bond reduction, and subunit composition. J. Biol. Chem. 254:58555861.
62. Merritt, E. A.,, and W. G. J. Hol. 1995. AB5 toxins. Curr. Opin. Struct. Biol. 5:165171.
63. Merritt, E. A.,, S. Sarfaty,, M. G. Jobling,, T. Chang,, R. K. Holmes,, T. R. Hirst,, and W. G. Hol. 1997. Structural studies of receptor binding by cholera toxin mutants. Protein Sci. 6:15161528.
64. Miesenbock, G.,, and J. E. Rothman. 1995. The capacity to retrieve escaped ER proteins extends to the trans-most cisterna of the Golgi stack. J. Cell Biol. 129:309319.
65. Montesano, R.,, J. Roth,, A. Robert,, and L. Orci. 1982. Non-coated membrane invaginations are involved in binding and internalization of cholera and tetanus toxins. Nature 296:651653.
66. Moss, J.,, and M. Vaughan. 1988. ADP-ribosylation of guanyl nucleotide-binding regulatory proteins by bacterial toxins. Adv. Enzymol. Relat. Areas Mol. Biol. 61:303379.
67. Moss, J.,, and M. Vaughan. 1977. Mechanism of action of choleragen: evidence for ADP-ribosyltransferase activity with arginine as an acceptor. J. Biol. Chem. 252:24552457.
68. Nashar, T. O.,, H. M. Webb,, S. Eaglestone,, N. A. Williams,, and T. R. Hirst. 1996. Potent immunogenicity of the B subunits of Escherichia coli heat-labile enterotoxin: receptor binding is essential and induces differential modulation of lymphocyte subsets. Proc. Nat. Acad. Sci. USA 93:226230.
69. O’Brien, A. D.,, V. L. Tesh,, A. Donohue-Rolfe,, M. P. Jackson,, S. Olsnes,, K. Sandvig,, A. A. Lindberg,, and G. T. Keusch. 1992. Shiga toxin: biochemistry, genetics, mode of action, and role in pathogenesis. Curr. Top. Microbiol. Immunol. 180:6594.
70. Oh, P.,, D. P. McIntosh,, and J. E. Schnitzer. 1998. Dynamin at the neck of caveolae mediates their budding to form transport vesicles by GTP-driven fission from the plasma membrane of endothelium. J. Cell Biol. 141:101114.
71. Orlandi, P. A. 1997. Protein-disulfide isomerase-mediated reduction of the A subunit of cholera toxin in a human intestinal cell line. J. Biol. Chem. 272:45914599.
72. Orlandi, P. A.,, P. K. Curran,, and P. H. Fishman. 1993. Brefeldin A blocks the response of cultured cells to cholera toxin: implications for intracellular trafficking in toxin action. J. Biol. Chem. 268:1201012016.
73. Orlandi, P. A.,, and P. H. Fishman. 1998. Filipin-dependent inhibition of cholera toxin: evidence for toxin internalization and activation through caveolae-like domains. J. Cell Biol. 141:905915.
74. Parton, R. G. 1996. Caveolae and caveolins. Cur. Opin. Cell Biol. 8:542548.
75. Parton, R. G. 1994. Ultrastructural localization of gangliosides; GM1 is concentrated in caveolae. J. Histo. Chem. Cytochem. 42:155166.
76. Parton, R. G.,, and K. Simons. 1995. Digging into caveolae. Science 269:13981399.
77. Pelham, H. R. B. 1990. The retention signal for soluble proteins of the endoplasmic reticulum. Trends Biochem. Sci. 15:483486.
78. Pelham, H. R. B.,, L. M. Roberts,, and M. Lord. 1992. Toxin entry: how reversible is the secretory pathway. Trends Cell Biol. 2:183185.
79. Pizza, M.,, M. Domenighini,, W. Hol,, V. Giannelli,, M. R. Fontana,, M. M. Giuliani,, C. Magagnoli,, S. Peppoloni,, R. Manetti,, and R. Rappuoli. 1994. Probing the structure-activity relationship of Escherichia coli LT-A by site-directed mutagenesis. Mol. Microbiol. 14:5160.
80. Ramegowda, B.,, and V. L. Tesh. 1996. Differentiation-associated toxin receptor modulation, cytokine production, and sensitivity to Shiga-like toxins in human monocytes and monocytic cell lines. Infect. Immun. 64:11731180.
81. Rodighiero, C.,, A. T. Aman,, M. J. Kenny,, J. Moss,, W. I. Lencer,, and T. R. Hirst. 1999. Structural basis for the differential toxicity of cholera toxin and Escherichia coli heat-labile enterotoxin. Construction of hybrid toxins identifies the A2-domain as the determinant of differential toxicity. J. Biol. Chem. 274:39623969.
82. Rodighiero, C.,, Y. Fujinaga,, T. R. Hirst,, and W. I. Lencer. 2001. A cholera toxin B-subunit variant that binds ganglioside G(M1) but fails to induce toxicity. J. Biol. Chem. 276:3693936945.
83. Ruddock, L. W.,, S. P. Ruston,, S. M. Kelly,, N. C. Price,, R. B. Freedman,, and T. R. Hirst. 1995. Kinetics of acid-mediated disassembly of the B subunit pentamer of Escherichia coli heat-labile enterotoxin. Molecular basis of pH stability. J. Biol. Chem. 270:2995329958.
84. Sandvig, K., Ø. Garred, K. Prydz, J. V. Kozlov, S. H. Hansen, and B. van Deurs. 1992. Retrograde transport of endocytosed Shiga toxin to the endoplasmic reticulum. Nature (London) 358:510511.
85. Sandvig, K.,, K. Prydz,, S. H. Hansen,, and B. van Deurs. 1991. Ricin transport in brefeldin A-treated cells: correlation between Golgi structure and toxic effect. J. Cell Biol. 115:971981.
86. Sandvig, K.,, M. Ryd, Ø. Garred, E. Schweda, P. K. Holm, and B. van Deurs. 1994. Retrograde transport from the Golgi complex to the ER of both Shiga toxin and the nontoxic Shiga B-fragment is regulated by buteric acid and cAMP. J. Cell Biol. 126:5364.
87. Sandvig, K.,, and B. van Deurs. 1996. Endocytosis, intracellular transport, and cytotoxic action of Shiga toxin and ricin. Physiol. Rev. 76:949966.
88. Schmitz, A.,, H. Herrgen,, A. Winkeler,, and V. Herzog. 2000. Cholera toxin is exported from microsomes by the sec61p complex. J. Cell Biol. 148:12031212.
89. Schnitzer, J. E.,, D. P. McIntosh,, A. M. Dvorak,, J. Liu,, and P. Oh. 1995. Separation of caveolae from associated microdomains of GPI-anchored proteins. Science 269:14351439.
90. Sears, C. L.,, and J. B. Kaper. 1996. Enteric bacterial toxins: mechanisms of action and linkage to intestinal secretion. Microbiol. Rev. 60:167215.
91. Simpson, J. C.,, L. M. Roberts,, K. Romisch,, J. Davey,, D. H. Wolf,, and J. M. Lord. 1999. Ricin A chain utilises the endoplasmic reticulum-associated protein degradation pathway to enter the cytosol of yeast. FEBS Lett. 459:8084.
92. Sixma, T. K.,, K. H. Kalk,, B. A. van Zanten,, Z. Dauter,, J. Kingma,, B. Witholt,, and W. G. Hol. 1993. Refined structure of Escherichia coli heat-labile enterotoxin, a close relative of cholera toxin. J. Mol. Biol. 230:890918.
93. Sixma, T. K.,, S. E. Pronk,, H. H. Kalk,, E. S. Wartna,, B. A. M. van Zanten,, B. Witholt,, and W. G. J. Hol. 1991. Crystal structure of a cholera toxin-related heat-labile enterotoxin from E. coli. Nature 351:371377.
94. Sixma, T. K.,, S. E. Pronk,, K. H. Kalk,, B. A. M. van Zanten,, A. M. Berghuis,, and W. G. J. Hol. 1992. Lactose binding to heat-labile enterotoxin revealed by X-ray crystallography. Nature 355:561564.
95. Spangler, B. D. 1992. Structure and function of cholera toxin and the related Escherichia coli heat-labile enterotoxin. Microb. Rev. 56:622647.
96. Tesh, V. L.,, B. Ramegowda,, and J. E. Samuel. 1994. Purified Shiga-like toxins induce expression of proinflammatory cytokines from murine peritoneal macrophages. Infect. Immun. 62:50855094.
97. Togawa, A.,, N. Morinaga,, M. Ogasawara,, J. Moss,, and M. Vaughan. 1999. Purification and cloning of a brefeldin A-inhibited guanine nucleotide-exchange protein for ADP-ribosylation factors. J. Biol. Chem. 274:1230812315.
98. Townsley, F. M.,, D. W. Wilson,, and H. R. Pelham. 1993. Mutational analysis of the human KDEL receptor: distinct structural requirements for Golgi retention, ligand binding and retrograde transport. EMBO J. 12:28212829.
99. Tsai, B.,, C. Rodighiero,, W. I. Lencer,, and T. Rapoport. 2001. Protein disulfide isomerase acts as a redox-dependent chaperone to unfold cholera toxin. Cell 104:937948.
100. Tsuji, T.,, T. Honda,, T. Miwatani,, S. Wakabayashi,, and H. Matsubara. 1985. Analysis of receptor-binding site in Escherichia coli enterotoxin. J. Biol. Chem. 260:85528558.
101. Tsuji, T.,, M. Kato,, H. Kawase,, S. Imamura,, H. Kamiya,, Y. Ichinose,, and A. Miyama. 1997. Escherichia coli LT enterotoxin subunit A demonstrates partial toxicity independent of the nicking around Arg192. Microbiology 143:17971804.
102. van Setten, P. A.,, L. A. Monnens,, R. G. Verstraten,, L. P. van den Heuvel,, and V. W. van Hinsbergh. 1996. Effects of verocytotoxin-1 on nonadherent human monocytes: binding characteristics, protein synthesis, and induction of cytokine release. Blood 88:174183.
103. Varma, R.,, and S. Mayor. 1998. GPI-anchored proteins are organized in submicron domains at the cell surface. Nature 394:798801.
104. Wilkinson, B. M.,, J. R. Tyson,, P. J. Reid,, and C. J. Stirling. 2000. Distinct domains within yeast Sec61p involved in posttranslational translocation and protein dislocation. J. Biol. Chem. 275:521529.
105. Wilson, D. W.,, M. J. Lewis,, and H. R. Pelham. 1993. pH-dependent binding of KDEL to its receptor in vitro. J. Biol. Chem. 268:74657468.
106. Wimer-Mackin, S.,, R. K. Holmes,, A. A. Wolf,, W. I. Lencer,, and M. G. Jobling. 2001. Characterization of receptor-mediated signal transduction by Escherichia coli Type IIa heat-labile enterotoxin in the polarized human intestinal cell line T84. Infect. Immun. 69:72057212.
107. Wolf, A. A.,, Y. A. Fujinaga,, and W. I. Lencer. 2002. Uncoupling of the cholera toxin GM1 ganglioside-receptor complex from endocytosis, retrograde Golgi trafficking, and downstream signal transduction by depletion of membrane cholesterol. J. Biol. Chem. 277:1624916256.
108. Wolf, A. A.,, M. G. Jobling,, S. Wimer-Mackin,, J. L. Madara,, R. K. Holmes,, and W. I. Lencer. 1998. Ganglioside structure dictates signal transduction by cholera toxin in polarized epithelia and association with caveolae-like membrane domains. J. Cell Biol. 141:917927.
109. Xuan-Cai, S. W.,, J. Q. Trojanowski,, and J. O. Gonatas. 1982. Cholera toxin and wheat germ agglutinin conjugates as neuroanatomical probes: their uptake and clearance, transganglionic and retrograde transport and sensitivity. Brain Res. 243:215224.
110. Zeller, C. B.,, and R. B. Marchase. 1992. Gangliosides as modulators of cell function. Am. J. Physiol. 262:C1341C1355.
111. Zhang, R.-G.,, M. L. Westbrook,, E. M. Westbrook,, D. L. Scott,, Z. Otwinowski,, P. R. Maulik,, R. A. Reed,, and G. G. Shipley. 1995. The 2.4 Å crystal structure of cholera toxin B subunit pentamer: choleragenoid. J. Mol. Biol. 251:550562.


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Selection of AB enterotoxins

Citation: Rodighiero C, Lencer W. 2003. Trafficking of Cholera Toxin and Related Bacterial Enterotoxins: Pathways and Endpoints, p 385-402. In Hecht G (ed), Microbial Pathogenesis and the Intestinal Epithelial Cell. ASM Press, Washington, DC. doi: 10.1128/9781555817848.ch21

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