Clostridium perfringens TpeL Induces Formation of Stress Fibers via Activation of RhoA-ROCK Signaling Pathway

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-term...

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Bibliographic Details
Published in:Biological & pharmaceutical bulletin 2015/05/01, Vol.38(5), pp.732-739
Main Authors: Nagahama, Masahiro, Ohkubo, Akiko, Kinouchi, Yoshihito, Kobayashi, Keiko, Miyamoto, Kazuaki, Takehara, Masaya, Sakurai, Jun
Format: Article
Language:English
Subjects:
Actins - metabolism
Amides - pharmacology
Animals
Bacterial Toxins - pharmacology
Clostridium Infections - metabolism
Clostridium perfringens
Clostridium perfringens - metabolism
Clostridium perfringens - pathogenicity
Clostridium perfringens TpeL
Dogs
Enzyme Inhibitors - pharmacology
Madin Darby Canine Kidney Cells
Pyridines - pharmacology
rac1 GTP-Binding Protein - metabolism
ras Proteins - metabolism
Rho A-Rho kinase (ROCK)
rho-Associated Kinases - metabolism
RhoA
rhoA GTP-Binding Protein - metabolism
Signal Transduction
stress fiber
Stress Fibers - metabolism
Transferases - pharmacology
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Summary: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.
ISSN:0918-6158
1347-5215
DOI:10.1248/bpb.b14-00842