title: Bordetella dermonecrotic toxin exerting toxicity through activation of the small GTPase Rho.
abstract: Bordetella dermonecrotic toxin (DNT) is a virulence factor produced by bacteria belonging to the genus Bordetella. The toxin possesses novel transglutaminase activity that catalyzes polyamination or deamidation of the small GTPases of the Rho family. The modified GTPases loose their GTP hydrolyzing activity, function as a constitutive active molecule, and continuously transduce signals to downstream effectors, which mediate the consequent phenotypes of cells intoxicated by DNT. A dynamin-dependent endocytosis is required for the toxin to be internalized into cells although it is unlikely transported to deep organelles such as the Golgi apparatus or the ER. Several lines of evidence show that the toxin undergoes proteolytic cleavage by furin or furin-like protease probably in the early endosome, and then escapes into the cytoplasm to reach the GTPase.
authors.affiliation: The Department of Bacterial Toxinology, Research Institute for Microbial Diseases, Osaka University, Yamada-oka 3-1, Suita, Osaka 565-0871, Japan.
authors.forename: Aya
authors.initials: A
authors.lastname: Fukui
authors.forename: Yasuhiko
authors.initials: Y
authors.lastname: Horiguchi
mesh_terms: D036002:ADP Ribose Transferases / Q000378:metabolism; D000818:Animals; D001427:Bacterial Toxins / Q000378:metabolism*; D001905:Botulinum Toxins / Q000378:metabolism; D003014:Clostridium botulinum / Q000378:metabolism; D003593:Cytoplasm / Q000378:metabolism; D034281:Dynamins / Q000737:chemistry; D004705:Endocytosis; D004721:Endoplasmic Reticulum / Q000378:metabolism; D045683:Furin / Q000737:chemistry; D006056:Golgi Apparatus / Q000378:metabolism; D006160:Guanosine Triphosphate / Q000737:chemistry; D006801:Humans; D006868:Hydrolysis; D008954:Models, Biological; D008956:Models, Chemical; D010641:Phenotype; D017434:Protein Structure, Tertiary; D015398:Signal Transduction; D011503:Transglutaminases / Q000378:metabolism*; D010566:Virulence Factors, Bordetella / Q000378:metabolism*; D020741:rho GTP-Binding Proteins / Q000737:chemistry*
chemical_list: D001427:Bacterial Toxins; D010566:Virulence Factors, Bordetella; C060969:dermonecrotic toxin, Bordetella; D006160:Guanosine Triphosphate; D011503:Transglutaminases; D036002:ADP Ribose Transferases; C063007:exoenzyme C3, Clostridium botulinum; D045683:Furin; D001905:Botulinum Toxins; D020741:rho GTP-Binding Proteins; D034281:Dynamins