Cholera toxin: a paradigm for multi-functional engagement of cellular mechanisms (Review).
Cholera toxin (Ctx) from Vibrio cholerae and its closely related homologue, heat-labile enterotoxin (Etx) from Escherichia coli have become superb tools for illuminating pathways of cellular trafficking and immune cell function. These bacterial protein toxins should be viewed as conglomerates of highly evolved, multi-functional elements equipped to engage the trafficking and signalling machineries of cells. Ctx and Etx are members of a larger family of A-B toxins of bacterial (and plant) origin that are comprised of structurally and functionally distinct enzymatically active A and receptor-binding B sub-units or domains. Intoxication of mammalian cells by Ctx and Etx involves B pentamer-mediated receptor binding and entry into a vesicular pathway, followed by translocation of the enzymatic A1 domain of the A sub-unit into the target cell cytosol, where covalent modification of intracellular targets leads to activation of adenylate cyclase and a sequence of events culminating in life-threatening diarrhoeal disease. Importantly, Ctx and Etx also have the capacity to induce a wide spectrum of remarkable immunological processes. With respect to the latter, it has been found that these toxins activate signalling pathways that modulate the immune system. This review explores the complexities of the cellular interactions that are engaged by these bacterial protein toxins, and highlights some of the new insights to have recently emerged.
De Haan
Lolke
L
Department of Pathology and Microbiology, School of Medical Sciences, University of Bristol, United Kingdom.
Hirst
Timothy R
TR
D000262:Adenylyl Cyclases / Q000378:metabolism; D000276:Adjuvants, Immunologic / Q000737:chemistry / Q000378:metabolism; D000818:Animals; D001426:Bacterial Proteins / Q000737:chemistry / Q000276:immunology / Q000378:metabolism; D001427:Bacterial Toxins / Q000737:chemistry / Q000276:immunology / Q000378:metabolism; D001693:Biological Transport, Active / Q000502:physiology; D002772:Cholera Toxin / Q000737:chemistry / Q000276:immunology / Q000378:metabolism; D003967:Diarrhea / Q000503:physiopathology; D004768:Enterotoxins / Q000737:chemistry / Q000276:immunology / Q000378:metabolism; D004926:Escherichia coli / Q000737:chemistry*; D029968:Escherichia coli Proteins; D006801:Humans; D007107:Immune System / Q000503:physiopathology; D011485:Protein Binding / Q000502:physiology; D017434:Protein Structure, Tertiary / Q000502:physiology; D021381:Protein Transport / Q000502:physiology; D015398:Signal Transduction / Q000502:physiology; D014734:Vibrio cholerae / Q000737:chemistry*
D000276:Adjuvants, Immunologic; D001426:Bacterial Proteins; D001427:Bacterial Toxins; D004768:Enterotoxins; D029968:Escherichia coli Proteins; D002772:Cholera Toxin; C027538:heat-labile enterotoxin, E coli; D000262:Adenylyl Cyclases