Pleiotropic role of Rac in mast cell activation revealed by a cell permeable Bordetella dermonecrotic fusion toxin

• Published in: Cellular signalling 2010-07, Vol.22 (7), p.1124-1131
• Main Authors: Stratmann, Heidi, Schwan, Carsten, Orth, Joachim H.C., Schmidt, Gudula, Aktories, Klaus
• Format: Article
• Language: English
• Subjects: Animals; Bordetella; Calcium; Calcium - metabolism; Cell Degranulation; Cell Line; Cell Membrane Permeability; Cells, Cultured; Clostridium difficile; Clostridium sordellii; Dermonecrotic toxin; Extracellular Signal-Regulated MAP Kinases - metabolism; Mast cell; Mast Cells - drug effects; Mast Cells - metabolism; Mast Cells - physiology; Mice; Peptides - genetics; Phospholipase Cγ; Rac; rac1 GTP-Binding Protein - drug effects; rac1 GTP-Binding Protein - physiology; Rats; Recombinant Fusion Proteins - pharmacology; rho GTP-Binding Proteins - metabolism; TAT fusion protein; Transglutaminases - genetics; Transglutaminases - pharmacology; Virulence Factors, Bordetella - genetics; Virulence Factors, Bordetella - pharmacology
• ISSN: 0898-6568; 1873-3913
• DOI: 10.1016/j.cellsig.2010.03.007

To activate the GTPase Rac in rat basophilic leukemia (RBL) cells and mouse bone marrow-derived mast cells (BMMC) a TAT fusion toxin of Bordetella dermonecrotic toxin (DNT-TAT) was constructed. The fusion toxin activated Rac1 and RhoA in vitro but only Rac in RBL cells and BMMC. DNT-TAT caused an increase in inositol phosphate formation, calcium mobilization, ERK activation and degranulation of mast cells. All these effects were inhibited by the Rho GTPase-inactivating Clostridium difficile toxin B and Clostridium sordellii lethal toxin. Also the calcium ionophore A23187 caused mast cell activation, including ERK phosphorylation, by processes involving an activation of Rac. The data indicate pleiotropic functions of Rac in mast cell activation.