ZFIN ID: ZDB-PUB-080227-11
The ATPase-dependent chaperoning activity of Hsp90a regulates thick filament formation and integration during skeletal muscle myofibrillogenesis
Hawkins, T.A., Haramis, A.P., Etard, C., Prodromou, C., Vaughan, C.K., Ashworth, R., Ray, S., Behra, M., Holder, N., Talbot, W.S., Pearl, L.H., Strähle, U., and Wilson, S.W.
Date: 2008
Source: Development (Cambridge, England)   135(6): 1147-1156 (Journal)
Registered Authors: Ashworth, Rachel, Behra, Martine, Etard, Christelle, Haramis, Anna-Pavlina, Hawkins, Tom, Holder, Nigel, Strähle, Uwe, Talbot, William S., Wilson, Steve
Keywords: Chaperones, Myofibrillogenesis, Zebrafish
MeSH Terms:
  • Adenosine Triphosphatases/chemistry
  • Adenosine Triphosphatases/deficiency
  • Adenosine Triphosphatases/genetics
  • Adenosine Triphosphatases/metabolism*
  • Animals
  • Base Sequence
  • Binding Sites
  • DNA Primers/genetics
  • HSP90 Heat-Shock Proteins/chemistry
  • HSP90 Heat-Shock Proteins/deficiency
  • HSP90 Heat-Shock Proteins/genetics
  • HSP90 Heat-Shock Proteins/metabolism*
  • Heat-Shock Response
  • Microscopy, Electron, Transmission
  • Models, Molecular
  • Muscle Development/physiology*
  • Muscle, Skeletal/growth & development*
  • Muscle, Skeletal/metabolism*
  • Mutation
  • Myofibrils/metabolism
  • Phenotype
  • Sarcomeres/metabolism
  • Zebrafish/genetics
  • Zebrafish/growth & development
  • Zebrafish/metabolism
  • Zebrafish Proteins/chemistry
  • Zebrafish Proteins/deficiency
  • Zebrafish Proteins/genetics
  • Zebrafish Proteins/metabolism*
PubMed: 18256191 Full text @ Development
The mechanisms that regulate sarcomere assembly during myofibril formation are poorly understood. In this study, we characterise the zebrafish sloth(u45) mutant, in which the initial steps in sarcomere assembly take place, but thick filaments are absent and filamentous I-Z-I brushes fail to align or adopt correct spacing. The mutation only affects skeletal muscle and mutant embryos show no other obvious phenotypes. Surprisingly, we find that the phenotype is due to mutation in one copy of a tandemly duplicated hsp90a gene. The mutation disrupts the chaperoning function of Hsp90a through interference with ATPase activity. Despite being located only 2 kb from hsp90a, hsp90a2 has no obvious role in sarcomere assembly. Loss of Hsp90a function leads to the downregulation of genes encoding sarcomeric proteins and upregulation of hsp90a and several other genes encoding proteins that may act with Hsp90a during sarcomere assembly. Our studies reveal a surprisingly specific developmental role for a single Hsp90 gene in a regulatory pathway controlling late steps in sarcomere assembly.