Proteolytic processing of myostatin is auto-regulated during myogenesis

McFarlane, Craig, Langley, Brett, Thomas, Mark, Hennebry, Alex, Plummer, Erin, Nicholas, Gina, McMahon, Chris, Sharma, Mridula, and Kambadur, Ravi (2005) Proteolytic processing of myostatin is auto-regulated during myogenesis. Developmental Biology, 283 (1). pp. 58-69.

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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.

Item ID: 52351
Item Type: Article (Research - C1)
ISSN: 1095-564X
Keywords: myostatin; myogenesis; processing; secretion; furin
Funders: Royal Society of New Zealand (RSNZ) Marsden Fund, Foundation of Research and Technology
Date Deposited: 06 Feb 2018 23:24
FoR Codes: 06 BIOLOGICAL SCIENCES > 0601 Biochemistry and Cell Biology > 060111 Signal Transduction @ 50%
06 BIOLOGICAL SCIENCES > 0601 Biochemistry and Cell Biology > 060103 Cell Development, Proliferation and Death @ 50%
SEO Codes: 97 EXPANDING KNOWLEDGE > 970106 Expanding Knowledge in the Biological Sciences @ 100%
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