Proteolytic processing of myostatin is auto-regulated during myogenesis
| Autor: | Mark Thomas, Mridula Sharma, Christopher D. McMahon, Alex Hennebry, Ravi Kambadur, Craig McFarlane, Erin Plummer, Brett Langley, Gina Nicholas |
|---|---|
| Rok vydání: | 2005 |
| Předmět: |
Proteases
Embryonic Development Myostatin Biology Processing Transfection Myoblasts Mice Western blot Genes Reporter Transforming Growth Factor beta medicine Myocyte Animals Homeostasis Northern blot RNA Messenger Promoter Regions Genetic Furin Molecular Biology Secretion medicine.diagnostic_test Myogenesis Gene Expression Regulation Developmental Cell Differentiation Cell Biology musculoskeletal system Molecular biology embryonic structures biology.protein Cattle Protein Processing Post-Translational Developmental Biology |
| Zdroj: | Developmental Biology. 283(1):58-69 |
| ISSN: | 0012-1606 |
| DOI: | 10.1016/j.ydbio.2005.03.039 |
| Popis: | Myostatin, a potent negative regulator of myogenesis, is proteolytically processed by furin proteases into active mature myostatin before secretion from myoblasts. Here, we show that mature myostatin auto-regulates its processing during myogenesis. In a cell culture model of myogenesis, Northern blot analysis revealed no appreciable change in myostatin mRNA levels between proliferating myoblasts and differentiated myotubes. However, Western blot analysis confirmed a relative reduction in myostatin processing and secretion by differentiated myotubes as compared to proliferating myoblasts. Furthermore, in vivo results demonstrate a lower level of myostatin processing during fetal muscle development when compared to postnatal adult muscle. Consequently, high levels of circulatory mature myostatin were detected in postnatal serum, while fetal circulatory myostatin levels were undetectable. Since Furin proteases are important for proteolytically processing members of the TGF-β superfamily, we therefore investigated the ability of myostatin to control the transcription of furin and auto-regulate the extent of its processing. Transfection experiments indicate that mature myostatin indeed regulates furin protease promoter activity. Based on these results, we propose a mechanism whereby myostatin negatively regulates its proteolytic processing during fetal development, ultimately facilitating the differentiation of myoblasts by controlling both furin protease gene expression and subsequent active concentrations of mature myostatin peptide. |
| Databáze: | OpenAIRE |
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