PUBLICATION

Troponin T is essential for sarcomere assembly in zebrafish skeletal muscle

Authors
Ferrante, M.I., Kiff, R.M., Goulding, D.A., and Stemple, D.L.
ID
ZDB-PUB-110124-2
Date
2011
Source
Journal of Cell Science   124(Pt 4): 565-577 (Journal)
Registered Authors
Stemple, Derek L.
Keywords
Muscle, Sarcomere, Troponin, Zebrafish
MeSH Terms
  • Actin Cytoskeleton/genetics
  • Actin Cytoskeleton/metabolism
  • Animals
  • Disease Models, Animal
  • Female
  • Humans
  • Male
  • Muscle, Skeletal/metabolism*
  • Myopathies, Nemaline/genetics
  • Myopathies, Nemaline/metabolism*
  • Myosins/genetics
  • Myosins/metabolism
  • Sarcomeres/genetics
  • Sarcomeres/metabolism*
  • Troponin T/genetics
  • Troponin T/metabolism*
  • Zebrafish/genetics
  • Zebrafish/metabolism*
  • Zebrafish Proteins/genetics
  • Zebrafish Proteins/metabolism*
PubMed
21245197 Full text @ J. Cell Sci.
Abstract
In striated muscle, the basic contractile unit is the sarcomere, which comprises myosin-rich thick filaments intercalated with thin filaments made of actin, tropomyosin and troponin. Troponin is required to regulate Ca(2+)-dependent contraction, and mutant forms of troponins are associated with muscle diseases. We have disrupted several genes simultaneously in zebrafish embryos and have followed the progression of muscle degeneration in the absence of troponin. Complete loss of troponin T activity leads to loss of sarcomere structure, in part owing to the destructive nature of deregulated actin-myosin activity. When troponin T and myosin activity are simultaneously disrupted, immature sarcomeres are rescued. However, tropomyosin fails to localise to sarcomeres, and intercalating thin filaments are missing from electron microscopic cross-sections, indicating that loss of troponin T affects thin filament composition. If troponin activity is only partially disrupted, myofibrils are formed but eventually disintegrate owing to deregulated actin-myosin activity. We conclude that the troponin complex has at least two distinct activities: regulation of actin-myosin activity and, independently, a role in the proper assembly of thin filaments. Our results also indicate that sarcomere assembly can occur in the absence of normal thin filaments.
Genes / Markers
Figures
Expression
Phenotype
Mutation and Transgenics
Human Disease / Model Data
Sequence Targeting Reagents
Fish
Antibodies
Orthology
Engineered Foreign Genes
Mapping
Errata and Notes