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Deletion of the Ste20-like kinase SLK in skeletal muscle results in a progressive myopathy and muscle weakness

Pryce Benjamin R., Al-Zahrani Khalid N., Dufresne Sébastien S., Belkina Natalya, Labrèche Cédrik, Patino-Lopez Genaro, Frenette Jérôme, Shaw Stephen et Sabourin Luc A.. (2017). Deletion of the Ste20-like kinase SLK in skeletal muscle results in a progressive myopathy and muscle weakness. Skeletal Muscle, 7, (3),

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URL officielle: https://doi.org/10.1186/s13395-016-0119-1

Résumé

Background The Ste20-like kinase, SLK, plays an important role in cell proliferation and cytoskeletal remodeling. In fibroblasts, SLK has been shown to respond to FAK/Src signaling and regulate focal adhesion turnover through Paxillin phosphorylation. Full-length SLK has also been shown to be essential for embryonic development. In myoblasts, the overexpression of a dominant negative SLK is sufficient to block myoblast fusion.

Methods In this study, we crossed the Myf5-Cre mouse model with our conditional SLK knockout model to delete SLK in skeletal muscle. A thorough analysis of skeletal muscle tissue was undertaken in order to identify defects in muscle development caused by the lack of SLK. Isometric force analysis was performed on adult knockout mice and compared to age-matched wild-type mice. Furthermore, cardiotoxin injections were performed followed by immunohistochemistry for myogenic markers to assess the efficiency muscle regeneration following SLK deletion.

Results We show here that early deletion of SLK from the myogenic lineage does not markedly impair skeletal muscle development but delays the regenerative process. Interestingly, adult mice (~6 months) display an increase in the proportion of central nuclei and increased p38 activation. Furthermore, mice as young as 3 months old present with decreased force generation, suggesting that the loss of SLK impairs myofiber stability and function. Assessment of structural components revealed aberrant localization of focal adhesion proteins, such as FAK and paxillin. Our data show that the loss of SLK results in unstable myofibers resulting in a progressive myopathy. Additionally, the loss of SLK resulted in a delay in muscle regeneration following cardiotoxin injections.

Conclusions Our results show that SLK is dispensable for muscle development and regeneration but is required for myofiber stability and optimal force generation.

Type de document:Article publié dans une revue avec comité d'évaluation
Volume:7
Numéro:3
Version évaluée par les pairs:Oui
Date:2017
Sujets:Sciences de la santé
Sciences de la santé > Sciences de l'activité physique et réadaptation
Sciences de la santé > Sciences de l'activité physique et réadaptation > Physiothérapie
Département, module, service et unité de recherche:Départements et modules > Département des sciences de la santé > Unité d'enseignement en physiothérapie
Mots-clés:Ste20-like kinase, myofiber stability, muscle regeneration
Déposé le:18 avr. 2019 21:35
Dernière modification:18 avr. 2019 21:35
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Creative Commons LicenseSauf indication contraire, les documents archivés dans Constellation sont rendus disponibles selon les termes de la licence Creative Commons "Paternité, pas d'utilisation commerciale, pas de modification" 2.5 Canada.

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