The UNC-45 chaperone mediates sarcomere assembly through myosin degradation in Caenorhabditis elegans.
The UNC-45 chaperone mediates sarcomere assembly through myosin degradation in Caenorhabditis elegans.
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UNC-45伴侣通过秀丽隐杆线虫中的肌球蛋白降解介导了肌动蛋白降解。
DOI：
10.1083/jcb.200607084
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发表时间：
2007-04-23
影响因子：
7.8
通讯作者：
Epstein, Henry F
中科院分区：
文献类型：
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作者：
Landsverk, Megan L;Li, Shumin;Hutagalung, Alex H;Najafov, Ayaz;Hoppe, Thorsten;Barral, Jose M;Epstein, Henry F
肌球蛋白马达是真核生物中多种细胞过程的核心。肌球蛋白伴侣蛋白ε-45的同源物已经涉及从真菌到人类的生物体中含肌球蛋白结构的组装和功能。在肌肉中，肌节肌球蛋白的组装被调节以产生稳定、均匀的粗丝。秀丽隐杆线虫中的功能丧失突变导致肌肉肌球蛋白积累减少和粗丝组装缺陷，导致动物瘫痪。我们报告说，转基因蠕虫过表达的α-45也显示缺陷，肌球蛋白组装，肌球蛋白含量减少和轻度瘫痪表型。我们发现，减少肌球蛋白的积累是通过泛素/蛋白酶体系统降解的结果。部分蛋白酶体抑制能够将肌球蛋白和蠕虫运动恢复到接近野生型水平。这些发现表明，在心力衰竭和肌肉萎缩等情况下，β-45相关蛋白可能有助于肌球蛋白降解的机制。
Myosin motors are central to diverse cellular processes in eukaryotes. Homologues of the myosin chaperone UNC-45 have been implicated in the assembly and function of myosin-containing structures in organisms from fungi to humans. In muscle, the assembly of sarcomeric myosin is regulated to produce stable, uniform thick filaments. Loss-of-function mutations in Caenorhabditis elegans UNC-45 lead to decreased muscle myosin accumulation and defective thick filament assembly, resulting in paralyzed animals. We report that transgenic worms overexpressing UNC-45 also display defects in myosin assembly, with decreased myosin content and a mild paralysis phenotype. We find that the reduced myosin accumulation is the result of degradation through the ubiquitin/proteasome system. Partial proteasome inhibition is able to restore myosin protein and worm motility to nearly wild-type levels. These findings suggest a mechanism in which UNC-45–related proteins may contribute to the degradation of myosin in conditions such as heart failure and muscle wasting.