RRC ID 61431
Author Nagahama M, Ohkubo A, Kinouchi Y, Kobayashi K, Miyamoto K, Takehara M, Sakurai J.
Title Clostridium perfringens TpeL Induces Formation of Stress Fibers via Activation of RhoA-ROCK Signaling Pathway.
Journal Biol Pharm Bull
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.
Volume 38(5)
Pages 732-9
Published 2015-1-1
DOI 10.1248/bpb.b14-00842
PMID 25947919
MeSH Actins / metabolism* Amides / pharmacology Animals Bacterial Toxins / pharmacology* Clostridium Infections / metabolism* Clostridium perfringens / metabolism Clostridium perfringens / pathogenicity* Dogs Enzyme Inhibitors / pharmacology Madin Darby Canine Kidney Cells Pyridines / pharmacology Signal Transduction Stress Fibers / metabolism* Transferases / pharmacology rac1 GTP-Binding Protein / metabolism ras Proteins / metabolism rho-Associated Kinases / metabolism* rhoA GTP-Binding Protein / metabolism*
IF 1.863
Human and Animal Cells MDCK(RCB0995)