PUBLICATION
Hsf1 is essential for proteotoxic stress response in smyd1b-deficient embryos and fish survival under heat shock
- Authors
- Xiao, H., Li, M., Zhong, Y., Patel, A., Xu, R., Zhang, C., Athey, T.W., Fang, S., Xu, T., Du, S.
- ID
- ZDB-PUB-250109-165
- Date
- 2025
- Source
- FASEB journal : official publication of the Federation of American Societies for Experimental Biology 39: e70283e70283 (Journal)
- Registered Authors
- Fang, Shengyun, Zhong, Yongwang
- Keywords
- Smyd1b, heat shock factor 1, heat shock protein, myofibril, stress response
- MeSH Terms
-
- Zebrafish Proteins*/deficiency
- Zebrafish Proteins*/genetics
- Zebrafish Proteins*/metabolism
- Proteotoxic Stress
- Animals
- Zebrafish*/embryology
- Zebrafish*/genetics
- HSP70 Heat-Shock Proteins/genetics
- HSP70 Heat-Shock Proteins/metabolism
- Muscle Proteins
- Heat Shock Transcription Factors/genetics
- Heat Shock Transcription Factors/metabolism
- Embryo, Nonmammalian/metabolism
- Gene Expression Regulation, Developmental
- Heat-Shock Response*/physiology
- PubMed
- 39760245 Full text @ FASEB J.
Citation
Xiao, H., Li, M., Zhong, Y., Patel, A., Xu, R., Zhang, C., Athey, T.W., Fang, S., Xu, T., Du, S. (2025) Hsf1 is essential for proteotoxic stress response in smyd1b-deficient embryos and fish survival under heat shock. FASEB journal : official publication of the Federation of American Societies for Experimental Biology. 39:e70283e70283.
Abstract
Molecular chaperones play critical roles in post-translational maintenance in protein homeostasis. Previous studies have shown that loss of Smyd1b function results in defective myofibril organization and dramatic upregulation of heat shock protein gene (hsp) expression in muscle cells of zebrafish embryos. To investigate the molecular mechanisms and functional importance of this stress response, we characterized changes of gene expression in smyd1b knockdown and knockout embryos using RNA-seq. The results showed that the top upregulated genes encode mostly cytosolic heat shock proteins. Co-IP assay revealed that the upregulated cytosolic Hsp70s associate with myosin chaperone UNC45b which is critical for myosin protein folding and sarcomere assembly. Strikingly, several hsp70 genes also display muscle-specific upregulation in response to heat shock-induced stress in zebrafish embryos. To investigate the regulation of hsp gene upregulation and its functional significance in muscle cells, we generated heat shock factor 1 (hsf-/-) knockout zebrafish mutants and analyzed hsp gene expression and muscle phenotype in the smyd1b-/-single and hsf1-/-;smyd1b-/- double-mutant embryos. The results showed that knockout of hsf1 blocked the hsp gene upregulation and worsened the muscle defects in smyd1b-/- mutant embryos. Moreover, we demonstrated that Hsf1 is essential for fish survival under heat shock (HS) conditions. Together, these studies uncover a correlation between Smyd1b deficiency and the Hsf1-activated heat shock response (HSR) in regulating muscle protein homeostasis and myofibril assembly and demonstrate that the Hsf1-mediated hsp gene upregulation is vital for the survival of zebrafish larvae under thermal stress conditions.
Genes / Markers
Expression
Phenotype
Mutations / Transgenics
Human Disease / Model
Sequence Targeting Reagents
Fish
Orthology
Engineered Foreign Genes
Mapping