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Myomesin is part of an integrity pathway that responds to sarcomere damage and disease


Autoři: Kendal Prill aff001;  Casey Carlisle aff002;  Megan Stannard aff003;  Pamela J. Windsor Reid aff004;  David B. Pilgrim aff003
Působiště autorů: Department of Molecular and Cellular Biology, University of Guelph, Guelph, Ontario, Canada aff001;  Department of Molecular Genetics, University of Toronto, Toronto, Ontario, Canada aff002;  Department of Biological Sciences, University of Alberta, Edmonton, Alberta, Canada aff003;  Department of Biological Sciences, MacEwan University, Edmonton, Alberta, Canada aff004
Vyšlo v časopise: PLoS ONE 14(10)
Kategorie: Research Article
doi: https://doi.org/10.1371/journal.pone.0224206

Souhrn

The structure and function of the sarcomere of striated muscle is well studied but the steps of sarcomere assembly and maintenance remain under-characterized. With the aid of chaperones and factors of the protein quality control system, muscle proteins can be folded and assembled into the contractile apparatus of the sarcomere. When sarcomere assembly is incomplete or the sarcomere becomes damaged, suites of chaperones and maintenance factors respond to repair the sarcomere. Here we show evidence of the importance of the M-line proteins, specifically myomesin, in the monitoring of sarcomere assembly and integrity in previously characterized zebrafish muscle mutants. We show that myomesin is one of the last proteins to be incorporated into the assembling sarcomere, and that in skeletal muscle, its incorporation requires connections with both titin and myosin. In diseased zebrafish sarcomeres, myomesin1a shows an early increase of gene expression, hours before chaperones respond to damaged muscle. We found that myomesin expression is also more specific to sarcomere damage than muscle creatine kinase, and our results and others support the use of myomesin assays as an early, specific, method of detecting muscle damage.

Klíčová slova:

Embryos – Muscle contraction – Muscle proteins – Myosins – Skeletal muscles – Structural proteins – Zebrafish


Zdroje

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