Distinct roles for Ste20-like kinase SLK in muscle function and regeneration
| Autor: | Sarah Kawesa, Paul O'Reilly, Marlene McKay, Luc A. Sabourin, Rashmi Kothary, Kate Daniel, Christopher J Storbeck, Roshan Sriram, Khalid N. Al-Zahrani, Catherine Tsilfidis |
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| Jazyk: | angličtina |
| Předmět: |
Muscle tissue
0303 health sciences Myogenesis Regeneration (biology) Research Motility Skeletal muscle Cell Biology Ste20-like Kinase Cell fate determination Biology Bioinformatics Transgenic Cell biology 03 medical and health sciences 0302 clinical medicine medicine.anatomical_structure medicine Orthopedics and Sports Medicine Kinase activity Molecular Biology 030217 neurology & neurosurgery Actin Muscle Regeneration 030304 developmental biology |
| Zdroj: | Skeletal Muscle |
| ISSN: | 2044-5040 |
| DOI: | 10.1186/2044-5040-3-16 |
| Popis: | Background Cell growth and terminal differentiation are controlled by complex signaling systems that regulate the tissue-specific expression of genes controlling cell fate and morphogenesis. We have previously reported that the Ste20-like kinase SLK is expressed in muscle tissue and is required for cell motility. However, the specific function of SLK in muscle tissue is still poorly understood. Methods To gain further insights into the role of SLK in differentiated muscles, we expressed a kinase-inactive SLK from the human skeletal muscle actin promoter. Transgenic muscles were surveyed for potential defects. Standard histological procedures and cardiotoxin-induced regeneration assays we used to investigate the role of SLK in myogenesis and muscle repair. Results High levels of kinase-inactive SLK in muscle tissue produced an overall decrease in SLK activity in muscle tissue, resulting in altered muscle organization, reduced litter sizes, and reduced breeding capacity. The transgenic mice did not show any differences in fiber-type distribution but displayed enhanced regeneration capacity in vivo and more robust differentiation in vitro. Conclusions Our results show that SLK activity is required for optimal muscle development in the embryo and muscle physiology in the adult. However, reduced kinase activity during muscle repair enhances regeneration and differentiation. Together, these results suggest complex and distinct roles for SLK in muscle development and function. |
| Databáze: | OpenAIRE |
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