In vivo modifications of small GTPase Rac and Cdc42 by Bordetella dermonecrotic toxin.
Bordetella dermonecrotic toxin (DNT) is known to activate the small GTPase Rho through deamidation or polyamination. In this study, we examined whether Rac and Cdc42, the two other members of the Rho family, serve as intracellular targets for the toxin. Immunoprecipitation and immunoblot assays revealed that DNT deamidated or polyaminated intracellular Rac and Cdc42. After the modifications, both Rac and Cdc42 lost their GTP-hydrolyzing, but not GTP-binding, activities. The interactions of the modified Rac and Cdc42 with their respective effectors were strictly dependent on GTP. MC3T3-E1 cells treated with DNT at high concentrations demonstrated extensive formations of lamellipodia and filopodia, which indicate the intracellular activation of Rac and Cdc42, respectively.
Masuda
Minako
M
Department of Bacterial Toxinology, Research Institute for Microbial Diseases, Osaka University, Suita, Osaka 565-0871, Japan.
Minami
Masayoshi
M
Shime
Hiroaki
H
Matsuzawa
Takeshi
T
Horiguchi
Yasuhiko
Y
D016475:3T3 Cells; D000818:Animals; D001427:Bacterial Toxins / Q000378:metabolism*; D001884:Bordetella / Q000201:enzymology*; D015870:Gene Expression; D051379:Mice; D009419:Nerve Tissue Proteins / Q000378:metabolism; D017346:Protein Serine-Threonine Kinases / Q000378:metabolism; D011503:Transglutaminases / Q000378:metabolism*; D010566:Virulence Factors, Bordetella; D051317:Wiskott-Aldrich Syndrome Protein, Neuronal; D020764:cdc42 GTP-Binding Protein / Q000235:genetics / Q000378:metabolism*; D054462:p21-Activated Kinases; D020744:rac GTP-Binding Proteins / Q000235:genetics / Q000378:metabolism*; D020741:rho GTP-Binding Proteins / Q000378:metabolism
D001427:Bacterial Toxins; D009419:Nerve Tissue Proteins; D010566:Virulence Factors, Bordetella; C495772:Wasl protein, mouse; D051317:Wiskott-Aldrich Syndrome Protein, Neuronal; C060969:dermonecrotic toxin, Bordetella; D011503:Transglutaminases; D017346:Protein Serine-Threonine Kinases; D054462:p21-Activated Kinases; D020764:cdc42 GTP-Binding Protein; D020744:rac GTP-Binding Proteins; D020741:rho GTP-Binding Proteins