Tropomyosin isoforms differentially affect muscle contractility in the head and body regions of the nematode Caenorhabditis elegans.
Tropomyosin isoforms differentially affect muscle contractility in the head and body regions of the nematode Caenorhabditis elegans.
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DOI：
10.1091/mbc.e17-03-0152
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发表时间：
2018-05-01
影响因子：
3.3
通讯作者：
Ono S
中科院分区：
文献类型：
--
作者：
Barnes DE;Watabe E;Ono K;Kwak E;Kuroyanagi H;Ono S
秀丽隐杆线虫有一个单一的基因lev-11，编码多种原肌球蛋白亚型。两个第七外显子在肌肉细胞的头部和体部区域中交替选择，并且差异地影响相应区域中的肌肉收缩性。原肌球蛋白是肌动蛋白的主要结合蛋白，调节肌动蛋白-肌球蛋白的相互作用和肌动蛋白-微丝的稳定性。多细胞生物表达多种原肌球蛋白亚型，但对亚型特异性原肌球蛋白功能的了解还不完全。秀丽隐杆线虫有一个单一的原肌球蛋白基因lev-11，据报道，它通过使用两个独立的启动子和选择性剪接表达四种异构体。在这里，我们报告了第五原肌球蛋白亚型，LEV-11 O，这是由选择性剪接，包括一个新发现的第七外显子，外显子7a。通过观察体内特定的剪接事件，我们发现外显子7a主要在头部的体壁肌肉的一个子集中被选择，而外显子7 b，这是外显子7a的替代品，在身体的其余部分被利用。外显子7a和外显子7 b中的点突变分别引起对左旋咪唑诱导的肌肉收缩的抗性，特别是在头部和主体中。LEV-11 O而非LEV-11 A在主体中的过表达导致弱的左旋咪唑抗性。这些结果表明，特定的原肌球蛋白异构体表达在头部和身体区域的肌肉和差异有助于调节肌肉收缩性。
The nematode Caenorhabditis elegans has a single gene, lev-11, encoding multiple tropomyosin isoforms. Two seventh exons are alternatively selected in the head and body regions of muscle cells and differentially affect muscle contractility in the respective regions. Tropomyosin, one of the major actin filament–binding proteins, regulates actin–myosin interaction and actin-filament stability. Multicellular organisms express a number of tropomyosin isoforms, but understanding of isoform-specific tropomyosin functions is incomplete. The nematode Caenorhabditis elegans has a single tropomyosin gene, lev-11, which has been reported to express four isoforms by using two separate promoters and alternative splicing. Here, we report a fifth tropomyosin isoform, LEV-11O, which is produced by alternative splicing that includes a newly identified seventh exon, exon 7a. By visualizing specific splicing events in vivo, we find that exon 7a is predominantly selected in a subset of the body wall muscles in the head, while exon 7b, which is the alternative to exon 7a, is utilized in the rest of the body. Point mutations in exon 7a and exon 7b cause resistance to levamisole-induced muscle contraction specifically in the head and the main body, respectively. Overexpression of LEV-11O, but not LEV-11A, in the main body results in weak levamisole resistance. These results demonstrate that specific tropomyosin isoforms are expressed in the head and body regions of the muscles and contribute differentially to the regulation of muscle contractility.