Biasing the conformation of ELMO2 reveals that myoblast fusion can be exploited to improve muscle regeneration
- Author
- Viviane Tran, Sarah Nahle, Amelie Robert, Ines Desanlis, Ryan Killoran, Sophie Ehresmann, Marie-Pier Thibault, David Barford, Kodi Ravichandran (UGent) , Martin Sauvageau, Matthew J. Smith, Marie Kmita and Jean-Francois Cote
- Organization
- Abstract
- Myoblast fusion is fundamental for the development of multinucleated myofibers. Evolutionarily conserved proteins required for myoblast fusion include RAC1 and its activator DOCK1. In the current study we analyzed the contribution of the DOCK1-interacting ELMO scaffold proteins to myoblast fusion. When Elmo1(-/-) mice underwent muscle-specific Elmo2 genetic ablation, they exhibited severe myoblast fusion defects. A mutation in the Elmo2 gene that reduced signaling resulted in a decrease in myoblast fusion. Conversely, a mutation in Elmo2 coding for a protein with an open conformation increased myoblast fusion during development and in muscle regeneration. Finally, we showed that the dystrophic features of the Dysferlin-null mice, a model of limb-girdle muscular dystrophy type 2B, were reversed when expressing ELMO2 in an open conformation. These data provide direct evidence that the myoblast fusion process could be exploited for regenerative purposes and improve the outcome of muscle diseases.
- Keywords
- NUCLEOTIDE EXCHANGE, CRKII/DOCK180/RAC PATHWAY, ACTIN CYTOSKELETON, CELL-MIGRATION, DYSFERLIN, GENE, EXPRESSION, PROTEINS, FAMILY, DOMAIN
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Citation
Please use this url to cite or link to this publication: http://hdl.handle.net/1854/LU-01GP15ZGJY05S1HJDS1HX4Q7W1
- MLA
- Tran, Viviane, et al. “Biasing the Conformation of ELMO2 Reveals That Myoblast Fusion Can Be Exploited to Improve Muscle Regeneration.” NATURE COMMUNICATIONS, vol. 13, no. 1, 2022, doi:10.1038/s41467-022-34806-4.
- APA
- Tran, V., Nahle, S., Robert, A., Desanlis, I., Killoran, R., Ehresmann, S., … Cote, J.-F. (2022). Biasing the conformation of ELMO2 reveals that myoblast fusion can be exploited to improve muscle regeneration. NATURE COMMUNICATIONS, 13(1). https://doi.org/10.1038/s41467-022-34806-4
- Chicago author-date
- Tran, Viviane, Sarah Nahle, Amelie Robert, Ines Desanlis, Ryan Killoran, Sophie Ehresmann, Marie-Pier Thibault, et al. 2022. “Biasing the Conformation of ELMO2 Reveals That Myoblast Fusion Can Be Exploited to Improve Muscle Regeneration.” NATURE COMMUNICATIONS 13 (1). https://doi.org/10.1038/s41467-022-34806-4.
- Chicago author-date (all authors)
- Tran, Viviane, Sarah Nahle, Amelie Robert, Ines Desanlis, Ryan Killoran, Sophie Ehresmann, Marie-Pier Thibault, David Barford, Kodi Ravichandran, Martin Sauvageau, Matthew J. Smith, Marie Kmita, and Jean-Francois Cote. 2022. “Biasing the Conformation of ELMO2 Reveals That Myoblast Fusion Can Be Exploited to Improve Muscle Regeneration.” NATURE COMMUNICATIONS 13 (1). doi:10.1038/s41467-022-34806-4.
- Vancouver
- 1.Tran V, Nahle S, Robert A, Desanlis I, Killoran R, Ehresmann S, et al. Biasing the conformation of ELMO2 reveals that myoblast fusion can be exploited to improve muscle regeneration. NATURE COMMUNICATIONS. 2022;13(1).
- IEEE
- [1]V. Tran et al., “Biasing the conformation of ELMO2 reveals that myoblast fusion can be exploited to improve muscle regeneration,” NATURE COMMUNICATIONS, vol. 13, no. 1, 2022.
@article{01GP15ZGJY05S1HJDS1HX4Q7W1,
abstract = {{Myoblast fusion is fundamental for the development of multinucleated myofibers. Evolutionarily conserved proteins required for myoblast fusion include RAC1 and its activator DOCK1. In the current study we analyzed the contribution of the DOCK1-interacting ELMO scaffold proteins to myoblast fusion. When Elmo1(-/-) mice underwent muscle-specific Elmo2 genetic ablation, they exhibited severe myoblast fusion defects. A mutation in the Elmo2 gene that reduced signaling resulted in a decrease in myoblast fusion. Conversely, a mutation in Elmo2 coding for a protein with an open conformation increased myoblast fusion during development and in muscle regeneration. Finally, we showed that the dystrophic features of the Dysferlin-null mice, a model of limb-girdle muscular dystrophy type 2B, were reversed when expressing ELMO2 in an open conformation. These data provide direct evidence that the myoblast fusion process could be exploited for regenerative purposes and improve the outcome of muscle diseases.}},
articleno = {{7077}},
author = {{Tran, Viviane and Nahle, Sarah and Robert, Amelie and Desanlis, Ines and Killoran, Ryan and Ehresmann, Sophie and Thibault, Marie-Pier and Barford, David and Ravichandran, Kodi and Sauvageau, Martin and Smith, Matthew J. and Kmita, Marie and Cote, Jean-Francois}},
issn = {{2041-1723}},
journal = {{NATURE COMMUNICATIONS}},
keywords = {{NUCLEOTIDE EXCHANGE,CRKII/DOCK180/RAC PATHWAY,ACTIN CYTOSKELETON,CELL-MIGRATION,DYSFERLIN,GENE,EXPRESSION,PROTEINS,FAMILY,DOMAIN}},
language = {{eng}},
number = {{1}},
pages = {{15}},
title = {{Biasing the conformation of ELMO2 reveals that myoblast fusion can be exploited to improve muscle regeneration}},
url = {{http://doi.org/10.1038/s41467-022-34806-4}},
volume = {{13}},
year = {{2022}},
}
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