Loss of Smyhc1 or Hsp90alpha1 function results in different effects on myofibril organization in skeletal muscles of zebrafish embryos.

Loss of Smyhc1 or Hsp90alpha1 function results in different effects on myofibril organization in skeletal muscles of zebrafish embryos.
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DOI:
10.1371/journal.pone.0008416
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发表时间:
2010-01-01
期刊:
影响因子:
3.7
通讯作者:
Du SJ
Du SJ
中科院分区:
综合性期刊3区
文献类型:
--
作者:
Codina M;Li J;Gutiérrez J;Kao JP;Du SJ

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肌原纤维发生需要肌节蛋白正确折叠和组装成高度组织化的肌节。热休克蛋白90α1(Heat shock protein 90 α1,Hsp 90 α1)是一种肌球蛋白伴侣,在肌原纤维形成中起重要作用。hsp 90 α1的敲除或突变导致粗丝和细丝以及M线和Z线结构的完全解体。目前尚不清楚这些肌节结构的解体是由于Hsp 90 α1功能丧失的直接影响,还是通过肌球蛋白粗丝的解体间接引起的。在这项研究中,我们通过基因特异性敲除或使用肌球蛋白ATP酶抑制剂BTS(N-苄基-对甲苯磺酰胺)在斑马鱼胚胎中进行了肌球蛋白粗丝功能丧失分析。我们证明,敲低肌球蛋白重链1(myhc 1)导致肌节缺陷的厚和薄的细丝和缺陷的Z线对齐。类似地,用BTS处理斑马鱼胚胎破坏了粗丝和细丝组织,对M线和Z线几乎没有影响。相反,Hsp 90 α1功能的丧失完全破坏了所有的肌节结构,包括粗丝和细丝以及M线和Z线。总之,这些研究表明,热休克蛋白90 α1的突变表型不是简单地由于破坏肌球蛋白折叠和组装,这表明热休克蛋白90 α1可能在其他肌节结构的组装和组织中发挥作用。
Myofibrillogenesis requires the correct folding and assembly of sarcomeric proteins into highly organized sarcomeres. Heat shock protein 90α1 (Hsp90α1) has been implicated as a myosin chaperone that plays a key role in myofibrillogenesis. Knockdown or mutation of hsp90α1 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 Hsp90α1 function or indirectly through the disorganization of myosin thick filaments. 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 Hsp90α1 function completely disrupted all sarcomeric structures including both thick and thin filaments as well as the M- and Z-lines. Together, these studies indicate that the hsp90α1 mutant phenotype is not simply due to disruption of myosin folding and assembly, suggesting that Hsp90α1 may play a role in the assembly and organization of other sarcomeric structures.
DOI: 10.1101/gad.2.10.1307
发表时间: 1988-10-01
影响因子: 10.5
作者:
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发表时间: 2008-01-15
影响因子: 11.1
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DOI: 10.1083/jcb.110.1.53
发表时间: 1990-01
期刊: The Journal of cell biology
影响因子: --
作者:
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通讯作者: Ishiwata S
DOI: 10.1083/jcb.107.6.2613
发表时间: 1988-12-01
影响因子: 7.8
作者:
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通讯作者: FALKENTHAL, S