Cytotoxic necrotizing factor 1 hinders skeletal muscle differentiation in vitro by perturbing the activation/deactivation balance of Rho GTPases
- 29 October 2004
- journal article
- Published by Springer Science and Business Media LLC in Cell Death & Differentiation
- Vol. 12 (1), 78-86
- https://doi.org/10.1038/sj.cdd.4401522
Abstract
The current knowledge assigns a crucial role to the Rho GTPases family (Rho, Rac, Cdc42) in the complex transductive pathway leading to skeletal muscle cell differentiation. Their exact function in myogenesis, however, remains largely undefined. The protein toxin CNF1 was herein employed as a tool to activate Rho, Rac and Cdc42 in the myogenic cell line C2C12. We demonstrated that CNF1 impaired myogenesis by affecting the muscle regulatory factors MyoD and myogenin and the structural protein MHC expressions. This was principally driven by Rac/Cdc42 activation whereas Rho apparently controlled only the fusion process. More importantly, we proved that a controlled balance between Rho and Rac/Cdc42 activation/deactivation state was crucial for the correct execution of the differentiation program, thus providing a novel view for the role of Rho GTPases in muscle cell differentiation. Also, the use of Rho hijacking toxins can represent a new strategy to pharmacologically influence the differentiative process.Keywords
This publication has 48 references indexed in Scilit:
- SHP-2 Positively Regulates Myogenesis by Coupling to the Rho GTPase Signaling PathwayMolecular and Cellular Biology, 2004
- Rac GTPase Instructs Nuclear Factor-κB Activation by Conveying the SCF Complex and IkBα to the Ruffling MembranesMolecular Biology of the Cell, 2004
- Actin Can Reorganize into Podosomes in Aortic Endothelial Cells, a Process Controlled by Cdc42 and RhoAMolecular and Cellular Biology, 2003
- Cytotoxic Necrotizing Factor 1 ofEscherichia coliStimulates Rho/Rho-Kinase-Dependent Myosin Light-Chain Phosphorylation without Inactivating Myosin Light-Chain Phosphatase in Endothelial CellsInfection and Immunity, 2003
- Rho GTPases in cell biologyNature, 2002
- Cadherin Engagement Regulates Rho family GTPasesJournal of Biological Chemistry, 2001
- RAC Regulation of Actin Polymerization and Proliferation by a Pathway Distinct from Jun KinaseScience, 1996
- Defining the regulatory networks for muscle developmentCurrent Opinion in Genetics & Development, 1996
- The small GTP-binding protein rac regulates growth factor-induced membrane rufflingCell, 1992
- The small GTP-binding protein rho regulates the assembly of focal adhesions and actin stress fibers in response to growth factorsCell, 1992