PMID:11032799

Citation	Fullner, KJ and Mekalanos, JJ (2000) In vivo covalent cross-linking of cellular actin by the Vibrio cholerae RTX toxin. EMBO J. 19:5315-23
Abstract	Enteric pathogens often export toxins that elicit diarrhea as a part of the etiology of disease, including toxins that affect cytoskeletal structure. Recently, we discovered that the intestinal pathogen Vibrio cholerae elicits rounding of epithelial cells that is dependent upon a gene we designated rtxA. Here we investigate the association of rtxA with the cell-rounding effect. We find that V. cholerae exports a large toxin, RTX (repeats-in-toxin) toxin, to culture supernatant fluids and that this toxin is responsible for cell rounding. Furthermore, we find that cell rounding is not due to necrosis, suggesting that RTX toxin is not a typical member of the RTX family of pore-forming toxins. Rather, RTX toxin causes depolymerization of actin stress fibers and covalent cross-linking of cellular actin into dimers, trimers and higher multimers. This RTX toxin-specific cross-linking occurs in cells previously rounded with cytochalasin D, indicating that G-actin is the toxin target. Although several models explain our observations, our simultaneous detection of actin cross-linking and depolymerization points toward a novel mechanism of action for RTX toxin, distinguishing it from all other known toxins.
Links	PubMed PMC314022 Online version:10.1093/emboj/19.20.5315
Keywords	ADP Ribose Transferases/metabolism; Actins/chemistry; Actins/metabolism; Adenosine Diphosphate Ribose/metabolism; Amino Acid Sequence; Antibodies/pharmacology; Bacterial Proteins/chemistry; Bacterial Proteins/metabolism; Blotting, Western; Botulinum Toxins; Cell Membrane Permeability/drug effects; Cell Size/drug effects; Cholera Toxin/chemistry; Cholera Toxin/metabolism; Cross-Linking Reagents/chemistry; Cross-Linking Reagents/metabolism; Culture Media, Conditioned/chemistry; Culture Media, Conditioned/metabolism; Cytochalasin D/pharmacology; Cytotoxins/chemistry; Cytotoxins/metabolism; Dimerization; Humans; Models, Biological; Molecular Sequence Data; Protein Binding; Sequence Alignment; Stress Fibers/drug effects; Tumor Cells, Cultured; Vibrio cholerae/chemistry; Vibrio cholerae/metabolism; Vibrio cholerae/pathogenicity; rho GTP-Binding Proteins/metabolism
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Annotations

Gene product	Qualifier	GO Term	Evidence Code	with/from	Aspect	Extension	Notes	Status
VIBCH:Q9KS12	part_of	GO:0005576: extracellular region	ECO:0000314: direct assay evidence used in manual assertion		C		Seeded From UniProt	complete
VIBCH:Q9KS12	involved_in	GO:0009405: pathogenesis	ECO:0000314: direct assay evidence used in manual assertion		P		Seeded From UniProt	complete
VIBCH:Q9KS12	involved_in	GO:0018262: isopeptide cross-linking	ECO:0000314: direct assay evidence used in manual assertion		P		Seeded From UniProt	complete
VIBCH:Q9KS12	involved_in	GO:0030042: actin filament depolymerization	ECO:0000314: direct assay evidence used in manual assertion		P		Seeded From UniProt	complete

References

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