Mutations in the Caenorhabditis elegans dystrophin-like gene dys-1 lead to hyperactivity and suggest a link with cholinergic transmission
Mutations in the Caenorhabditis elegans dystrophin-like gene dys-1 lead to hyperactivity and suggest a link with cholinergic transmission
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DOI：
10.1007/s100480050053
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发表时间：
1998-12-01
期刊：
影响因子：
2.2
通讯作者：
Ségalat, L
中科院分区：
文献类型：
--
作者：
Bessou, C;Giugia, JB;Ségalat, L
人类营养不良蛋白基因的突变会导致杜氏肌营养不良症，这是一种常见的神经肌肉疾病，会导致肌肉细胞的进行性坏死。这种坏死的病因尚不清楚，dystrophin蛋白的细胞功能也尚不清楚。我们在秀丽线虫中发现了一个类似dystrophin的基因(命名为dys-1)，dys-1基因的功能缺失突变使动物过度活跃和轻微过度收缩，令人惊讶的是，dys-1突变体具有明显的正常肌肉细胞。根据报告基因分析和异源启动子的表达，dys-1基因的作用部位似乎在肌肉中。其中蛋白质的C末端被人的dystrophin序列取代的嵌合转基因能够部分抑制dys-1突变体的表型，表明这两个蛋白质有一些功能相似之处，最后，dys-1突变体对乙酰胆碱和乙酰胆碱酯酶抑制物灭威过敏，表明dys-1突变影响胆碱能传递，本研究提供了dystrophin家族蛋白与胆碱能传递之间的第一个功能联系。
Mutations in the human dystrophin gene cause Duchenne muscular dystrophy, a common neuromuscular disease leading to a progressive necrosis of muscle cells. The etiology of this necrosis has not been clearly established, and the cellular function of the dystrophin protein is still unknown. We report here the identification of a dystrophin-like gene (named dys-1) in the nematode Caenorhabditis elegans, Loss-of-function mutations of the dys-1 gene make animals hyperactive and slightly hypercontracted, Surprisingly, the dys-1 mutants have apparently normal muscle cells. Based on reporter gene analysis and heterologous promoter expression, the site of action of the dys-1 gene seems to be in muscles. A chimeric transgene in which the C-terminal end of the protein has been replaced by the human dystrophin sequence is able to partly suppress the phenotype of the dys-1 mutants, showing that both proteins share some functional similarity, Finally, the dys-1 mutants are hypersensitive to acetylcholine and to the acetylcholinesterase inhibitor aldicarb, suggesting that dys-1 mutations affect cholinergic transmission, This study provides the first functional link between the dystrophin family of proteins and cholinergic transmission.