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

*Center of Marine Biotechnology and
^‡Medical Biotechnology Center, University of Maryland Biotechnology Institute, 701 East Pratt Street, Baltimore, MD 21202

Edited by Eric N. Olson, University of Texas Southwestern Medical Center, Dallas, TX, and approved November 28, 2007 (received for review August 3, 2007)

Abstract

Heat-shock protein 90α (Hsp90α) is a member of the molecular chaperone family involved in protein folding and assembly. The role of Hsp90α in the developmental process, however, remains unclear. Here we report that zebrafish contains two Hsp90α genes, Hsp90α1, and Hsp90α2. Hsp90α1 is specifically expressed in developing somites and skeletal muscles of zebrafish embryos. We have demonstrated that Hsp90α1 is essential for myofibril organization in skeletal muscles of zebrafish embryos. Knockdown of Hsp90α1 resulted in paralyzed zebrafish embryos with poorly organized myofibrils in skeletal muscles. In contrast, knockdown of Hsp90α2 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 Hsp90α1. Biochemical analyses revealed that knockdown of Hsp90α1 resulted in significant myosin degradation and up-regulation of unc-45b gene expression. These results indicate that Hsp90α1 plays an important role in muscle development, likely through facilitating myosin folding and assembly into organized myofibril filaments.

Footnotes

^†To whom correspondence should be addressed. E-mail: dus{at}umbi.umd.edu
Author contributions: S.J.D. designed research; S.J.D., H.L., Y.B., and Y.Z. performed research; S.J.D. analyzed data; and S.J.D. wrote the paper.
The authors declare no conflict of interest.
This article is a PNAS Direct Submission.
This article contains supporting information online at www.pnas.org/cgi/content/full/0707330105/DC1.