title: Clostridium perfringens TpeL Induces Formation of Stress Fibers via Activation of RhoA-ROCK Signaling Pathway.
abstract: Clostridium perfringens TpeL belongs to a family of large clostridial glucosylating cytotoxins. TpeL modifies Rac1 and Ras subfamily proteins. Herein we report TpeL-induced formation of stress fibers via RhoA-Rho kinase (ROCK) signaling. A recombinant protein (TpeL1-525) derived from the TpeL N-terminal catalytic domain in the presence of streptolysin O (SLO) induced the formation of actin stress fibers in Madin-Darby canine kidney (MDCK) cells in a dose-dependent manner. The RhoA/ROCK pathway is known to control the formation of stress fibers. We examined the role of the RhoA/ROCK pathway in TpeL-induced formation of stress fibers. TpeL1-525-induced formation of stress fibers was inhibited by the ROCK inhibitor, Y27632 and Rho protein inhibitor, C3 transferase. TpeL1-525 activated RhoA and ROCK in a dose-dependent manner. C3 transferase blocked TpeL1-525-induced activation of RhoA and ROCK whereas Y27632 inhibited TpeL-induced activation of ROCK. These results demonstrate for the first time that TpeL induces the formation of stress fibers by activating the RhoA/ROCK signaling pathway.
authors.affiliation: Department of Microbiology, Faculty of Pharmaceutical Sciences, Tokushima Bunri University.
authors.forename: Masahiro
authors.initials: M
authors.lastname: Nagahama
authors.forename: Akiko
authors.initials: A
authors.lastname: Ohkubo
authors.forename: Yoshihito
authors.initials: Y
authors.lastname: Kinouchi
authors.forename: Keiko
authors.initials: K
authors.lastname: Kobayashi
authors.forename: Kazuaki
authors.initials: K
authors.lastname: Miyamoto
authors.forename: Masaya
authors.initials: M
authors.lastname: Takehara
authors.forename: Jun
authors.initials: J
authors.lastname: Sakurai
mesh_terms: D000199:Actins / Q000378:metabolism*; D000577:Amides / Q000494:pharmacology; D000818:Animals; D001427:Bacterial Toxins / Q000494:pharmacology*; D003015:Clostridium Infections / Q000378:metabolism*; D003016:Clostridium perfringens / Q000378:metabolism / Q000472:pathogenicity*; D004285:Dogs; D004791:Enzyme Inhibitors / Q000494:pharmacology; D061985:Madin Darby Canine Kidney Cells; D011725:Pyridines / Q000494:pharmacology; D015398:Signal Transduction; D022502:Stress Fibers / Q000378:metabolism*; D014166:Transferases / Q000494:pharmacology; D020830:rac1 GTP-Binding Protein / Q000378:metabolism; D018631:ras Proteins / Q000378:metabolism; D054460:rho-Associated Kinases / Q000378:metabolism*; D020742:rhoA GTP-Binding Protein / Q000378:metabolism*
chemical_list: D000199:Actins; D000577:Amides; D001427:Bacterial Toxins; D004791:Enzyme Inhibitors; D011725:Pyridines; C108830:Y 27632; D014166:Transferases; D054460:rho-Associated Kinases; D020830:rac1 GTP-Binding Protein; D018631:ras Proteins; D020742:rhoA GTP-Binding Protein