Produced by Vibrio cholerae, cholera toxin (CT) is a multimeric enterotoxin that transfers ADP-ribose to a G protein, locking adenylate cyclase in an 'on' position.
- How does Cholera Toxin cause diarrhea? By binding to the membrane of enteric cells, cholera toxin stimulates the cellular adenylate cyclase system, causing the hyper-secretion of chloride and bicarbonate ions, which results in increased fluid secretion and the severe diarrhea characteristic of the disease cholera. The pentameric B subunit of CT binds with high efficiency to GM1 monosialoganglioside cell membrane receptors, present in many cell types, allowing its use experimentally in cell culture. Following binding, the toxin is endocytosed and travels retrogradely to the endoplasmic reticulum where the enzymatically active A subunit (CTA1) is translocated to the cytosol. Within the cytosol, CTA1 catalyzes the ADP-ribosylation of the Gs protein, which activates adenylate cyclase and as a consequence increasing the intracellular concentration of cAMP.
- How is Cholera Toxin used in vaccine adjuvant development? Relevant to the development of vaccine adjuvants, CT effectively modulates mammalian immune systems and acts as an adjuvant for co-administered antigens.
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