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Mechanism of Action of Choleragen: Effect of Toxin on Binding of Guanyl Nucleotides

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Bacterial Diarrheal Diseases

Part of the book series: New Perspectives in Clinical Microbiology ((NPCM,volume 9))

Abstract

Choleragen (cholera toxin), the enterotoxin produced by Vibrio cholerae which is in large part responsible for the symptomatology of cholera, exerts its effects on cells through the activation of adenylate cyclase, resulting in an increase in intracellular cAMP(1–3). Adenylate cyclase, a membrane-bound, multisubunit system, consists of at least three components: a specific hormone receptor, a guanyl nucleotide-binding protein referred to as G/F, and a catalytic unit(4, 5). The hormone receptors are necessary for the binding of specific agonists to the cell membrane and are responsible, for example, for the effect of certain prostaglandins and peptide hormones on intracellular cAMP(4); the catalytic unit is responsible for the conversion of ATP to cAMP(6, 7), and G/F is necessary for the coupling of receptor and catalytic unit as well as for the activation of catalytic unit by guanyl nucleotides(4, 5).

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References

  1. Finkelstein, R. A. 1973. Cholera. CRC Crit. Rev. Microbiol. 2: 553–623.

    Article  CAS  Google Scholar 

  2. Moss, J., and M. Vaughan. 1979. Activation of adenylate cyclase by choleragen. Ann. Rev. Biochem. 48: 581–600.

    Article  PubMed  CAS  Google Scholar 

  3. Holmgren, J. 1981. Actions of cholera toxin and the prevention and treatment of cholera. Nature 292: 413–417.

    Article  PubMed  CAS  Google Scholar 

  4. Rodbell, M. 1980. The role of hormone receptors and GTP-regulatory proteins in membrane transduction. Nature 284: 17–22.

    Article  PubMed  CAS  Google Scholar 

  5. Ross, E. M., and A. G. Gilman. 1980. Biochemical properties of hormone-sensitive adenylate cyclase. Ann. Rev. Biochem. 49: 533–564.

    Article  PubMed  CAS  Google Scholar 

  6. Strittmatter, S., and E. J. Neer. 1980. Properties of the separated catalytic and regulatory units of brain adenylate cyclase. Proc. Natl. Acad. Sci. U.S.A. 77: 6344–6348.

    Article  PubMed  CAS  Google Scholar 

  7. Ross, E. M. 1981. Physical separation of the catalytic and regulatory proteins of hepatic adenylate cyclase. J. Biol. Chem. 256: 1949–1953.

    PubMed  CAS  Google Scholar 

  8. Rodbell, M., L. Birnbaumer, S. L. Pohl, and H. M. J. Krans. 1971. The glucagon-sensitive adenylate cyclase system in plasma membrane of rat liver. V. The obligatory role of guanyl nucleotides in glucagon action. J. Biol. Chem. 246: 1877–1882.

    PubMed  CAS  Google Scholar 

  9. Moss, J., and M. Vaughan. 1981. Mechanism of action of choleragen and E. coli heat-labile enterotoxin: Activation of adenylate cyclase by ADP-ribosylation. Mol. Cell. Biochem. 37: 75–90.

    CAS  Google Scholar 

  10. Enomoto, K., and D. M. Gill. 1980. Cholera toxin activation of adenylate cyclase. J. Biol. Chem. 255: 1252–1258.

    PubMed  CAS  Google Scholar 

  11. Moss, J., and M. Vaughan. 1977. Choleragen activation of solubilized adenylate cyclase: Requirement for GTP and protein activator for demonstration of enzymatic activity. Proc. Natl. Acad. Sci. U.S.A. 74: 4396–4400.

    Article  PubMed  CAS  Google Scholar 

  12. Lin, M. C., A. F. Welton, and M. F. Berman. 1978. Essential role of GTP in the expression of adenylate cyclase activity after cholera toxin treatment. J. Cyclic Nucleotide Res. 4: 159–168.

    PubMed  CAS  Google Scholar 

  13. Nakaya, S., J. Moss, and M. Vaughan. 1980. Effects of nucleotide triphosphates on choleragen-activated brain adenylate cyclase. Biochemistry 19: 4871–4874.

    Article  PubMed  CAS  Google Scholar 

  14. Cassel, D., and Z. Selinger. 1976. Catecholamine-stimulated GTPase activity in turkey erythrocyte membranes. Biochem. Biophys. Acta 452: 538–551.

    PubMed  CAS  Google Scholar 

  15. Cassel, P., and Z. Selinger. 1977. Mechanism of adenylate cyclase activation by cholera toxin: Inhibition of GTP hydrolysis at the regulatory site. Proc. Natl. Acad. Sci. U.S.A. 74: 3307–3311.

    Article  PubMed  CAS  Google Scholar 

  16. Cassel, D., and Z. Selinger. 1978. Mechanism of adenylate cyclase activation through the (3-adrenergic receptor: Catecholamine-induced displacement of bound GDP by GTP. Proc. Natl. Acad. Sci. U.S.A. 75: 4155–4159.

    Article  PubMed  CAS  Google Scholar 

  17. Pike. L. J., and R. J. Lefkowitz. 1981. Correlation of β-adrenergic receptor-stimulated [3H]GDP release and adenylate cyclase activation. J. Biol. Chem. 256: 2207–2212.

    PubMed  CAS  Google Scholar 

  18. Burns, D. L., J. Moss, and M. Vaughan. 1982. Choleragen-stimulated release of guanyl nucleotides from turkey erythrocyte membranes. J. Biol. Chem. 257: 32–34.

    PubMed  CAS  Google Scholar 

  19. Moss, J., J. C. Osborne, Jr., P. H. Fishman, H. B. Brewer, Jr., M. Vaughan, and R. O. Brady. 1977. Effect of gangliosides and substrate analogues on the hydrolysis of nicotinamide adenine dinucleotide by choleragen. Proc. Natl. Acad. Sci. U.S.A. 74: 74–78.

    Article  PubMed  CAS  Google Scholar 

  20. Gill, D. M. 1975. Involvement of nicotinamide adenine dinucleotide in the action of cholera toxin in vitro. Proc. Natl. Acad. Sci. U.S.A. 72: 2064–2068.

    Article  PubMed  CAS  Google Scholar 

  21. Burns, D. L., J. Moss, and M. Vaughan. 1982. Choleragen accelerates release of guanyl nucleotides from the GTP-binding protein of adenylate cyclase. Fed. Proc. 41: 5075.

    Google Scholar 

  22. Pfeuffer, T. 1977. GTP-binding proteins in membranes and the control of adenylate cyclase activity. J. Biol. Chem. 252: 7224–7234.

    PubMed  CAS  Google Scholar 

  23. Maguire, M. E., E. M. Ross, and A. G. Gilman. 1977. β-adrenergic receptor: Ligand binding properties and the interaction with adenyl cyclase. Adv. Cyclic Nucleotide Res. 8: 1–83.

    PubMed  CAS  Google Scholar 

  24. Cassel, D., and Z. Selinger. 1977. Catecholamine-induced release of [3H]Gpp(NH)p from turkey erythrocyte adenylate cyclase. J. Cyclic Nucleotide Res. 3: 11–22.

    PubMed  CAS  Google Scholar 

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© 1985 KTK Scientific Publishers, Tokyo

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Moss, J., Burns, D.L., Vaughan, M. (1985). Mechanism of Action of Choleragen: Effect of Toxin on Binding of Guanyl Nucleotides. In: Takeda, Y., Miwatani, T. (eds) Bacterial Diarrheal Diseases. New Perspectives in Clinical Microbiology, vol 9. Springer, Dordrecht. https://doi.org/10.1007/978-94-009-4990-4_15

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  • DOI: https://doi.org/10.1007/978-94-009-4990-4_15

  • Publisher Name: Springer, Dordrecht

  • Print ISBN: 978-94-010-8709-4

  • Online ISBN: 978-94-009-4990-4

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