Functional analysis of slow myosin heavy chain 1 and myomesin-3 in sarcomere organization in zebrafish embryonic slow muscles.

Functional analysis of slow myosin heavy chain 1 and myomesin-3 in sarcomere organization in zebrafish embryonic slow muscles.
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DOI:
10.1016/j.jgg.2012.01.005
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发表时间:
2012-02
影响因子:
5.9
通讯作者:
Du, Shao Jun
Du, Shao Jun
中科院分区:
生物学2区
文献类型:
--
作者:
Xu, Jin;Gao, Jie;Li, Junling;Xue, Liangyi;Clark, Karl J.;Ekker, Stephen C.;Du, Shao Jun

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肌原纤维形成是肌节形成的过程,需要肌节蛋白和肌节结构的各种成分的密切相互作用。肌球蛋白粗丝和M线是肌节的两个关键组成部分。已有研究表明,M系的肌球蛋白与肌球蛋白和肌动蛋白相互作用,使粗丝和肌动蛋白保持有序。然而,肌球蛋白在肌原纤维形成和肌节组织中的作用在很大程度上仍然是个谜。目前还没有关于肌球蛋白在体内肌节组织中的作用的基因敲除或基因敲除动物模型的报道。在这项研究中,通过在斑马鱼胚胎中使用基因特异性敲除的方法,我们对肌球蛋白-3和慢肌球蛋白重链1(Smyhc1)进行了功能丧失分析,该基因在慢肌中特异表达。我们证明,敲除smyhc1基因消除了肌球蛋白-3在慢肌中的肌小节定位。相反,肌球蛋白-3的缺失对粗丝和细丝的肌节组织以及M线和Z线结构没有影响。综上所述,这些研究表明,肌球蛋白粗丝是肌球蛋白-3的M线组织和M线定位所必需的。相反,在缓慢的肌肉中,肌球蛋白-3对于肌节的组织是必不可少的。
Myofibrillogenesis, the process of sarcomere formation, requires close interactions of sarcomeric proteins and various components of sarcomere structures. The myosin thick filaments and M-lines are two key components of the sarcomere. It has been suggested that myomesin proteins of M-lines interact with myosin and titin proteins and keep the thick and titin filaments in order. However, the function of myomesin in myofibrillogenesis and sarcomere organization remained largely enigmatic. No knockout or knockdown animal models have been reported to elucidate the role of myomesin in sarcomere organization in vivo. In this study, by using the gene-specific knockdown approach in zebrafish embryos, we carried out a loss-of-function analysis of myomesin-3 and slow myosin heavy chain 1 (smyhc1) expressed specifically in slow muscles. We demonstrated that knockdown of smyhc1 abolished the sarcomeric localization of myomesin-3 in slow muscles. In contrast, loss of myomesin-3 had no effect on the sarcomeric organization of thick and thin filaments as well as M- and Z-line structures. Together, these studies indicate that myosin thick filaments are required for M-line organization and M-line localization of myomesin-3. In contrast, myomesin-3 is dispensable for sarcomere organization in slow muscles.
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