Heat-shock protein 90α1 is required for organized myofibril assembly in skeletal muscles of zebrafish embryos
Heat-shock protein 90α1 is required for organized myofibril assembly in skeletal muscles of zebrafish embryos
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DOI：
10.1073/pnas.0707330105
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发表时间：
2008-01-15
影响因子：
11.1
通讯作者：
Zhong, Yongwang
中科院分区：
文献类型：
--
作者：
Du, Shao Jun;Li, Huiqing;Zhong, Yongwang
热休克蛋白90 α（Hsp 90 α）是参与蛋白质折叠和组装的分子伴侣家族的成员。然而，Hsp 90 α在发育过程中的作用仍不清楚。在这里，我们报告说，斑马鱼含有两个热休克蛋白90 α基因，热休克蛋白90 α 1，和热休克蛋白90 α 2。热休克蛋白90 α 1在斑马鱼胚胎体节和骨骼肌发育中特异表达。我们已经证明，热休克蛋白90 α 1是必不可少的肌原纤维组织在骨骼肌的斑马鱼胚胎。Hsp 90 α 1的敲低导致斑马鱼胚胎瘫痪，骨骼肌中的肌原纤维组织不良。相反，Hsp 90 α 2的敲低对肌肉收缩和肌原纤维组织没有影响。丝缺陷可以通过Hsp 90 α 1的异位表达以细胞自主的方式被拯救。生化分析表明，敲低HSP 90 α 1导致显着的肌球蛋白降解和上调unc-45 b基因的表达。这些结果表明，Hsp 90 α 1在肌肉发育中起着重要作用，可能是通过促进肌球蛋白折叠和组装成有组织的肌原纤维丝。
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.