PUBLICATION

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

Authors
Prill, K., Carlisle, C., Stannard, M., Windsor Reid, P.J., Pilgrim, D.B.
ID
ZDB-PUB-191024-6
Date
2019
Source
PLoS One   14: e0224206 (Journal)
Registered Authors
Carlisle, Casey, Pilgrim, David
Keywords
none
MeSH Terms
  • Animals
  • Animals, Genetically Modified/genetics
  • Animals, Genetically Modified/growth & development
  • Animals, Genetically Modified/metabolism
  • Connectin/genetics
  • Connectin/metabolism*
  • Heart/physiology*
  • Muscle, Skeletal/metabolism*
  • Muscle, Skeletal/pathology
  • Muscular Diseases/metabolism*
  • Muscular Diseases/pathology
  • Sarcomeres/metabolism*
  • Sarcomeres/pathology
  • Zebrafish/genetics
  • Zebrafish/growth & development
  • Zebrafish/metabolism*
  • Zebrafish Proteins/genetics
  • Zebrafish Proteins/metabolism*
PubMed
31644553 Full text @ PLoS One
Abstract
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.
Genes / Markers
Figures
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Expression
Phenotype
Mutations / Transgenics
Human Disease / Model
Sequence Targeting Reagents
Fish
Antibodies
Orthology
Engineered Foreign Genes
Mapping