Cholera Entry into cells

Lencer Wl, de Almeida JB, Moe S, etal. (1993) Entry of cholera toxin into polarized human intestinal epithelial cells Identification of an early brefeldin A-sensitive event required for Ai-peptide generation. In J. Clin. Invest. 92 2941-2951. 

Gangliosides are receptors for specific agents, such as cholera toxin and influenza virus. Cholera toxin binds to ganglioside GMl, whereas influenza virus recognizes the sialic acid portion of certain gangliosides. The influenza virus then cleaves the gangliosides as part of its entry process into cells. 

Protein toxins acting intracellularly are often composed of two subunits (A/B model). One subunit is catalytic (A-subunit) and the other is responsible for binding and cell entry (B-subunit). Following binding to an extracellular membrane receptor, the toxins are endocytosed. From the endosomes, the A-subunit is directly (pH dqDendent) transferred into the cytosol (e.g., diphtheria toxin and anthrax toxin) or the toxin is transported in a retrograde manner via the golgi to the ER (e.g., cholera toxin), where translocation into the cytosol occurs [1]. 

Vibrio cholera, the bacterium that causes cholera, colonizes the small intestine and produces cholera enterotoxin, which, as a consequence, brings about various symptoms including watery diarrhea. Cholera toxin is made up of a single A subunit of 27 kDa (CTA) and a nontoxic pentamer of B subunits of 11.6 kDa (CTB) together, these form a hexameric multi mer (Daniell et al., 2001). The A subunit has ADP ribosyl-transferase activity and facilitates entry of the toxin into epithelial cells. When administered... 

Detailed molecular features as well as events leading to the integration of toxins into lipid bilayers is not clear at this point, and is a subject of intense current research. While the available knowledge of the structure of a handful toxins such as cholera, Psudomonas exotoxin A and porin, some common factors are visible, no toxic motif(s) has been identified yet. Availability of three dimensional structure of an adequate number of toxins is likely to reveal interesting structural features. Another area of needed research is the characterization of receptors for toxins. In most cases, cell surface receptors hold the key of toxin entry and potency. Receptor knowledge will not only help develop antidotes against toxins, but also could also help our understanding of toxins themselves. 

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