Chapter 15 : Epithelial Response to Enteric Pathogens: Activation of Chloride Secretory Pathways

MyBook is a cheap paperback edition of the original book and will be sold at uniform, low price.

Preview this chapter:
Zoom in

Epithelial Response to Enteric Pathogens: Activation of Chloride Secretory Pathways, Page 1 of 2

| /docserver/preview/fulltext/10.1128/9781555817848/9781555812614_Chap15-1.gif /docserver/preview/fulltext/10.1128/9781555817848/9781555812614_Chap15-2.gif


This chapter focuses on the disruption of transcellular chloride secretion by microbial pathogens, with emphasis on recent advances in this field. A brief review of normal chloride secretion is outlined in the chapter. Mutations in the cystic fibrosis transmembrane conductance regulator (CFTR) gene that lead to mislocalization, altered function, or expression of this protein have serious pathophysiological consequences. Cholera toxin (CT) from and the type I and type II heat-labile enterotoxins (LTI and LTII) from are the primary agents that mediate the diarrhea caused by these organisms. These toxins belong to the AB5 enterotoxin family. , the leading cause of nosocomial enteric infections, is a noninvasive pathogen that causes colitis entirely by the action of two potent exotoxins, toxin A and toxin B. Unlike CT and enterotoxin, which elicit secretion without an acute inflammatory component, toxin triggers marked intestinal inflammation. In the normal intestine, increases in cyclic guanosine monophosphate (cGMP) lead to the phosphorylation and activation of the CFTR by the membrane-bound cGMP-dependent protein kinase II (PKGII) or by cross-activation of the cyclic AMP (cAMP)-dependent protein kinase. Calcium-dependent chloride secretion is a transient response even in the continued presence of the agonist. Secretion via the transcellular pathway is an exquisitely regulated process. Various pathogens and their toxins can directly disrupt these pathways, frequently by invoking multiple mechanisms.

Citation: Viswanathan V, Hecht G. 2003. Epithelial Response to Enteric Pathogens: Activation of Chloride Secretory Pathways, p 267-284. In Hecht G (ed), Microbial Pathogenesis and the Intestinal Epithelial Cell. ASM Press, Washington, DC. doi: 10.1128/9781555817848.ch15

Key Concept Ranking

Bacterial Proteins
Bacterial Pathogenesis
Bacterial Virulence Factors
Cholera Toxin
Highlighted Text: Show | Hide
Loading full text...

Full text loading...


Image of FIGURE 1

Intestinal epithelial cells display a polarized distribution of various ion transporters. Electroneutral transport of chloride across the basolateral surface is primarily driven by the sodium concentration gradient established by the NaK ATPase. Potassium channels on the basolateral surface are involved in potassium recycling, thereby preventing cellular depolarization. Accumulation of chloride within the cell beyond its electrochemical equilibrium is the electrical driving force for chloride movement across apical chloride channels. While the bulk of this transport occurs via the CFTR, the CaCC also contribute, especially toward acute secretory responses. The intermediate messengers cAMP and cGMP potentiate chloride secretion by acting primarily on CFTR and NKCC1. Figure adapted from Barrett and Keely ( ).

Citation: Viswanathan V, Hecht G. 2003. Epithelial Response to Enteric Pathogens: Activation of Chloride Secretory Pathways, p 267-284. In Hecht G (ed), Microbial Pathogenesis and the Intestinal Epithelial Cell. ASM Press, Washington, DC. doi: 10.1128/9781555817848.ch15
Permissions and Reprints Request Permissions
Download as Powerpoint
Image of FIGURE 2

Cholera toxin and the heat-labile toxins bind to ganglioside receptors and enter epithelial cells as an AB5 complex by retrograde membrane trafficking through the Golgi and ER. Dissociation and cleavage of the A subunit result in the A1-peptide-mediated ADPribosylation of G . This results in a sustained activation of adenylate cyclase and elevation of cAMP, which in turn increases electrogenic chloride secretion.

Citation: Viswanathan V, Hecht G. 2003. Epithelial Response to Enteric Pathogens: Activation of Chloride Secretory Pathways, p 267-284. In Hecht G (ed), Microbial Pathogenesis and the Intestinal Epithelial Cell. ASM Press, Washington, DC. doi: 10.1128/9781555817848.ch15
Permissions and Reprints Request Permissions
Download as Powerpoint
Image of FIGURE 3

toxins A and B bind to an as yet undefined receptor on human intestinal epithelial cells and enter cells via an endosomal compartment. These toxins inactivate low-molecular-weight GTPases of the Rho family by glucosylation. In addition, the toxins rapidly localize to the mitochondria, leading to cytotoxic effects. The effect of toxin A on secretion may involve the induction of COX-2-mediated elevation of PGE levels. PGE, in turn, is known to induce cAMP-mediated chloride secretion in intestinal epithelial cells.

Citation: Viswanathan V, Hecht G. 2003. Epithelial Response to Enteric Pathogens: Activation of Chloride Secretory Pathways, p 267-284. In Hecht G (ed), Microbial Pathogenesis and the Intestinal Epithelial Cell. ASM Press, Washington, DC. doi: 10.1128/9781555817848.ch15
Permissions and Reprints Request Permissions
Download as Powerpoint
Image of FIGURE 4

Guanylin, uroguanylin, and the homologous peptides from bacteria, EAST-1 and ST, bind to the guanylate cyclase C receptor, leading to the production of cGMP. cGMP mediates the phosphorylation and activation of CFTR by either the cGMP-or cAMP-dependent protein kinase.

Citation: Viswanathan V, Hecht G. 2003. Epithelial Response to Enteric Pathogens: Activation of Chloride Secretory Pathways, p 267-284. In Hecht G (ed), Microbial Pathogenesis and the Intestinal Epithelial Cell. ASM Press, Washington, DC. doi: 10.1128/9781555817848.ch15
Permissions and Reprints Request Permissions
Download as Powerpoint
Image of FIGURE 5

TDH and TDH-related hemolysin of and NSP4 of rotavirus elevate intracellular calcium concentrations by a protein kinase C-dependent mechanism. This results in the activation of the CaCC.

Citation: Viswanathan V, Hecht G. 2003. Epithelial Response to Enteric Pathogens: Activation of Chloride Secretory Pathways, p 267-284. In Hecht G (ed), Microbial Pathogenesis and the Intestinal Epithelial Cell. ASM Press, Washington, DC. doi: 10.1128/9781555817848.ch15
Permissions and Reprints Request Permissions
Download as Powerpoint
Image of FIGURE 6

Phosphorylated inositol derivatives are involved in regulating Ca-mediated chloride secretion and may have stimulatory or inhibitory effects. Derivatives such as Ins(3,4,5)P3 inhibit basolateral potassium channels, thereby elevating the positive charge within the cell, thus favoring the retention of chloride ions within the cell. Proteins injected into epithelial cells by sp. promote the production of Ins(1,4,5,6)P4, which in turn blocks Ins(3,4,5)P-mediated K channel inhibition. In addition, the protein SopB also hydrolyzes Ins(3,4,5)P. Removal of K channel inhibition results in the export of potassium ions and renders the cell with a net negative charge, thereby favoring the exit of chloride ions through the apical channels.

Citation: Viswanathan V, Hecht G. 2003. Epithelial Response to Enteric Pathogens: Activation of Chloride Secretory Pathways, p 267-284. In Hecht G (ed), Microbial Pathogenesis and the Intestinal Epithelial Cell. ASM Press, Washington, DC. doi: 10.1128/9781555817848.ch15
Permissions and Reprints Request Permissions
Download as Powerpoint


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 proteasomemediated 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. ADPribosylation 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 cellsurface 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. Dynaminmediated 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 KDELbearing 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. So ling. 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. ADPribosylation 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 ADPribosyltransferase 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 GTPdriven 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 structureactivity 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 Bsubunit 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 heatlabile 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 ADPribosylation 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. GPIanchored 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.


Generic image for table

Modulators of chloride secretion pathways

Citation: Viswanathan V, Hecht G. 2003. Epithelial Response to Enteric Pathogens: Activation of Chloride Secretory Pathways, p 267-284. In Hecht G (ed), Microbial Pathogenesis and the Intestinal Epithelial Cell. ASM Press, Washington, DC. doi: 10.1128/9781555817848.ch15
Generic image for table

Citation: Viswanathan V, Hecht G. 2003. Epithelial Response to Enteric Pathogens: Activation of Chloride Secretory Pathways, p 267-284. In Hecht G (ed), Microbial Pathogenesis and the Intestinal Epithelial Cell. ASM Press, Washington, DC. doi: 10.1128/9781555817848.ch15

This is a required field
Please enter a valid email address
Please check the format of the address you have entered.
Approval was a Success
Invalid data
An Error Occurred
Approval was partially successful, following selected items could not be processed due to error