Heat-shock protein 90α1 is required for organized myofibril assembly in skeletal muscles of zebrafish embryos

Heat-shock protein 90 alpha (Hsp90 alpha) is a member of the molecular chaperone family involved in protein folding and assembly. The role of Hsp90 alpha in the developmental process, however, remains unclear. Here we report that zebrafish contains two Hsp90 alpha genes, Hsp90 alpha 1, and Hsp90 alpha 2. Hsp90 alpha 1 is specifically expressed in developing somites and skeletal muscles of zebrafish embryos. We have demonstrated that Hsp90 alpha 1 is essential for myofibril organization in skeletal muscles of zebrafish embryos. Knockdown of Hsp90 alpha 1 resulted in paralyzed zebrafish embryos with poorly organized myofibrils in skeletal muscles. In contrast, knockdown of Hsp90 alpha 2 had no effect on muscle contraction and myofibril organization. The filament defects could be rescued in a cell autonomous manner by an ectopic expression of Hsp90 alpha 1. Biochemical analyses revealed that knockdown of Hsp90 alpha 1 resulted in significant myosin degradation and up-regulation of unc-45b gene expression. These results indicate that Hsp90 alpha 1 plays an important role in muscle development, likely through facilitating myosin folding and assembly into organized myofibril filaments.