title: Loss of Smyhc1 or Hsp90alpha1 function results in different effects on myofibril organization in skeletal muscles of zebrafish embryos.
abstract: BACKGROUND
  Myofibrillogenesis requires the correct folding and assembly of sarcomeric proteins into highly organized sarcomeres. Heat shock protein 90alpha1 (Hsp90alpha1) has been implicated as a myosin chaperone that plays a key role in myofibrillogenesis. Knockdown or mutation of hsp90alpha1 resulted in complete disorganization of thick and thin filaments and M- and Z-line structures. It is not clear whether the disorganization of these sarcomeric structures is due to a direct effect from loss of Hsp90alpha1 function or indirectly through the disorganization of myosin thick filaments.
  
  
  RESULTS
  In this study, we carried out a loss-of-function analysis of myosin thick filaments via gene-specific knockdown or using a myosin ATPase inhibitor BTS (N-benzyl-p-toluene sulphonamide) in zebrafish embryos. We demonstrated that knockdown of myosin heavy chain 1 (myhc1) resulted in sarcomeric defects in the thick and thin filaments and defective alignment of Z-lines. Similarly, treating zebrafish embryos with BTS disrupted thick and thin filament organization, with little effect on the M- and Z-lines. In contrast, loss of Hsp90alpha1 function completely disrupted all sarcomeric structures including both thick and thin filaments as well as the M- and Z-lines.
  
  
  CONCLUSIONS
  Together, these studies indicate that the hsp90alpha1 mutant phenotype is not simply due to disruption of myosin folding and assembly, suggesting that Hsp90alpha1 may play a role in the assembly and organization of other sarcomeric structures.
authors.affiliation: Center of Marine Biotechnology, Biotechnology Institute, University of Maryland, Baltimore, Maryland, United States of America.
authors.forename: Marta
authors.initials: M
authors.lastname: Codina
authors.forename: Junling
authors.initials: J
authors.lastname: Li
authors.forename: Joaquim
authors.initials: J
authors.lastname: Gutiérrez
authors.forename: Joseph P Y
authors.initials: JP
authors.lastname: Kao
authors.forename: Shao Jun
authors.initials: SJ
authors.lastname: Du
mesh_terms: D000818:Animals; D055785:Gene Knockdown Techniques; D018841:HSP90 Heat-Shock Proteins / Q000235:genetics / Q000502:physiology*; D018482:Muscle, Skeletal / Q000196:embryology* / Q000378:metabolism; D018995:Myosin Heavy Chains / Q000235:genetics / Q000502:physiology*; D015027:Zebrafish / Q000196:embryology*
chemical_list: D018841:HSP90 Heat-Shock Proteins; D018995:Myosin Heavy Chains