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.
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Abbreviations
- MRFs:
-
muscle-restricted regulatory factors
- SRF:
-
serum response factor
- CNF1:
-
cytotoxic necrotizing factor 1
- GM:
-
growth medium
- DM:
-
differentiation medium
- MHC:
-
myosin heavy chain
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Acknowledgements
We are grateful to W Malorni for critical reading of the manuscript and useful suggestions and to MG Quaranta for the densitometry analysis. The work has been partially supported by grants from ISS (project ‘Bacterial protein toxins as pharmacological agents that act on muscle cell differentiation’) to CF and from CNR/MIUR (project ‘Biomolecole per la salute umana’) and University of Rome ‘La Sapienza’ to MG.
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Travaglione, S., Messina, G., Fabbri, A. et al. Cytotoxic necrotizing factor 1 hinders skeletal muscle differentiation in vitro by perturbing the activation/deactivation balance of Rho GTPases. Cell Death Differ 12, 78–86 (2005). https://doi.org/10.1038/sj.cdd.4401522
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DOI: https://doi.org/10.1038/sj.cdd.4401522
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