Cholera toxin

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Contents

Introduction

Cholera Toxin (CT) is a protein secreted by the bacterium Vibrio choleraeUNIQ1c03b9ea41c06445-nowiki-00000001-QINU1UNIQ1c03b9ea41c06445-nowiki-00000002-QINU. is spread by dirty water and characterised by its ability to cause severe diarrhoea, often leading to dehydration[2].

Structure of the Toxin 

CT is a member of the AB5 family of toxins and consists of two subunits, Alpha and Beta. The Beta subunit binds to five ganglioslide GM1 receptors on the plasma membrane and trigers endocytosis of the toxin, whilst the Alpha subunit is made up of an A1 and A2 chain. These are cleaved apart once inside the cell, allowing the A1 chain to dissociate and begin its catalytic activity, leaving the A2 domain which had been anchoring the A1 chain to the Beta subunit[3].  

How CT Causes Disease

Following the toxins entry into the cell and Alpha protomer cleavage, the A1 is trafficked to theendoplasmic reticulum (ER) where it associates with disulphide isomerase (PDI). This triggers the unfolding of the A1 chain and consequently allows it to hijack the ER association degradation mechanism to enter the cytosol by retro-translocation. Normally, proteins which enter the cytosol in this manner are ubiquitinated and then degraded by the proteasome, however, the A1 subunit avoids this fate by rapid refolding[4].

The A1 can now ribosylates the alpha subunit of a G-protein associated with an intestinal epithelial cell, preventing the hydrolysis of GTP bound to the same G-protein. This locks the G-protein in an active state, leading to the indefinite stimulation of adenylyl cyclase, causing a rise in cAMP concentration. This then causes water and Cl- to leave the cell and enter the intestinal lumen, leading to the severe diarrhoea[5].

References

  1. Vanden Broeck D, H. C. D. W. M., 2007. Vibrio cholerae: cholera toxin. Int J Biochem Cell Biol, 39(10), pp. 1771-1775.
  2. Dilip Kumar Biswas, Rama Bhunia, Dipankar Maji, and Palash Das, “Contaminated Pond Water Favors Cholera Outbreak at Haibatpur Village, Purba Medinipur District, West Bengal, India,” Journal of Tropical Medicine, vol. 2014, Article ID 764530, 5 pages, 2014. doi:10.1155/2014/764530
  3. Daniel J.-F. Chinnapen, H. C. D. S. W. I. L., 2006. Rafting with cholera toxin: endocytosis and trafficking from plasma membrane to ER. FEMS Microbiology Letters, 266(2), pp. 129-137.
  4. Naomi L. B. Wernick, D. J.-F. C. A. C. a. W. I. L., 2010. Cholera Toxin: An Intracellular Journey into the Cytosol by Way of the Endoplasmic Reticulum. MDPI, 2(3), pp. 310-325.
  5. Bruce Alberts, A. J. J. L. M. R. K. R. a. P. W., 2007. Molecular Biology of the Cell, 5th edition. In: Molecular Biology of the Cell, 5th edition. New York: Garland Science, p. 906.
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