Price Maureen G, Landsverk Megan L, Barral Jose M, Epstein Henry F
Department of Neurology, Baylor College of Medicine, Houston, TX 77030, USA.
J Cell Sci. 2002 Nov 1;115(Pt 21):4013-23. doi: 10.1242/jcs.00108.
Previous studies have shown that the UNC-45 protein of C. elegans is required for normal thick filament assembly, binds Hsp90 and the myosin head, and shows molecular chaperone activity. We report here that mice and humans each have two genes that are located on different chromosomes, encode distinct UNC-45-like protein isoforms, and are expressed either in multiple tissues or only in cardiac and skeletal muscles. Their expression is regulated during muscle differentiation in vitro, with the striated muscle isoform mRNA appearing during myoblast fusion. Antisense experiments in C2C12 skeletal myogenic cells demonstrate that decreasing the general cell isoform mRNA reduces proliferation and fusion, while decreasing the striated muscle isoform mRNA affects fusion and sarcomere organization. These results suggest that the general cell UNC-45 isoform may have primarily cytoskeletal functions and that the striated muscle UNC-45 isoform may be restricted to roles in muscle-specific differentiation.
先前的研究表明，秀丽隐杆线虫的UNC-45蛋白是正常粗肌丝组装所必需的，它能结合Hsp90和肌球蛋白头部，并具有分子伴侣活性。我们在此报告，小鼠和人类各有两个位于不同染色体上的基因，它们编码不同的UNC-45样蛋白异构体，且在多种组织中表达，或仅在心肌和骨骼肌中表达。它们的表达在体外肌肉分化过程中受到调控，横纹肌异构体mRNA在成肌细胞融合时出现。在C2C12骨骼肌成肌细胞中进行的反义实验表明，降低一般细胞异构体mRNA会减少增殖和融合，而降低横纹肌异构体mRNA则会影响融合和肌节组织。这些结果表明，一般细胞UNC-45异构体可能主要具有细胞骨架功能，而横纹肌UNC-45异构体可能仅限于在肌肉特异性分化中发挥作用。
