Myosin Quality Control Systems in Zebrafish Skeletal Muscle Development
Bibliographic record
Abstract
In order to maintain homeostasis, defective proteins must be identified, removed, and replaced. In skeletal muscle, failures in this process can lead to a variety of incurable muscle diseases (myopathies), many of which are fatal. While aspects of protein turnover have been studied widely, the protein turnover process in skeletal muscle is still incompletely understood, especially with respect to the motor protein, myosin. By studying the assembly and maintenance of the basic unit of striated muscle, the sarcomere, we aim to elucidate the components involved and the mechanism controlling muscle myosin quality control in skeletal muscle. Zebrafish make an excellent model system to study sarcomere protein turnover due to their ability to survive with myopathies that are fatal in other organisms. Using two different zebrafish lines, steif , and herzschlag , we and others show that steif sarcomeres fail to assemble myosin thick filaments due to a loss of a critical component (Etard et al ., 2007), while herzschlag sarcomeres degrade over time as a consequence of muscle contractions. Transmission electron microscopy coupled with H&E staining revealed a slow muscle atrophy specific to herzschlag embryos. To identify factors involved in response to myosin damage during assembly or maintenance, we have screened through candidate genes, myosin chaperones and muscle specific E3 enzymes, using in situ hybridization and qPCR. Our data indicates a division of function where specific E3 enzymes and myosin chaperones respond to myosin damage exclusively during assembly, while other E3 enzymes respond to myosin damage during sarcomere maintenance. Pharmaceutical inhibition of the proteasome shifts this response in steif embryos, but not herzschlag , suggesting an interconnected network of protein quality control during myosin assembly. Together, this work helps highlight potential therapeutic targets to treat myosin turnover related myopathies. Support or Funding Information NSERC This abstract is from the Experimental Biology 2019 Meeting. There is no full text article associated with this abstract published in The FASEB Journal .
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How this classification was reachedexpand
Full frame machine prediction
Teacher imitationNot calibrated prevalence, not ground truth. Human validation pending. The Gemma side is a direct model label for every work in the frame, read from the title-only record. The Codex side is a classifier learned from the 10,348 direct Codex labels and calibrated to design-weighted sample rates; fields without enough sample support carry no Codex call. Candidate is the union of the two sides; consensus is their intersection. These outputs are machine_predicted_unvalidated and are not human labels.
Distilled classifier scores by category (both heads)
| Category | Codex | Gemma |
|---|---|---|
| Metaresearch | 0.000 | 0.000 |
| Meta-epidemiology (narrow) | 0.000 | 0.000 |
| Meta-epidemiology (broad) | 0.000 | 0.000 |
| Bibliometrics | 0.001 | 0.000 |
| Science and technology studies | 0.000 | 0.000 |
| Scholarly communication | 0.000 | 0.000 |
| Open science | 0.001 | 0.001 |
| Research integrity | 0.001 | 0.001 |
| Insufficient payload (model declined to judge) | 0.002 | 0.001 |
Machine scores (provisional)
The two teacher heads of the student model, read on this work. A score orders the frame for review; it never asserts a category, and the validation status ships verbatim with every row.
Baseline scores from an immature model (maturity gate not passed, 7 training rounds). Scores rank; they never assert a category.
score_only:v0-immature-baseline · verbatim from the scoring run: score_only means the number may rank works, and no category label ships from itClassification
machine, unvalidatedMachine predicted; a candidate call from one source (direct Gemma or distilled Codex), not a consensus.
How this classification was reached, model by model and score by score, is at the end of the page under "How this classification was reached".