Nitric-oxide synthase is a mechanical signal transducer that modulates talin and vinculin expression
Nitric-oxide synthase is a mechanical signal transducer that modulates talin and vinculin expression
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DOI：
10.1074/jbc.274.46.33155
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发表时间：
1999-11-12
影响因子：
4.8
通讯作者：
Lavergne, E
中科院分区：
文献类型：
--
作者：
Tidball, JG;Spencer, MJ;Lavergne, E
机械刺激可以引起肌肉质量和结构的变化，这表明存在将机械刺激转换为影响基因表达的信号的机制。肌腱接头显示出对改变的肌肉负荷的适应，这表明这些是肌纤维中转录上不同的结构域，可能经历对集中在这些位点的结构蛋白表达的局部调节。talin和talin是细胞骨架蛋白，它们在我们假设受到局部转录调控的肌腱连接处高度富集。我们的研究结果表明，在体内和体外的肌肉细胞的机械刺激引起的黏着斑蛋白和talin的表达是由一氧化氮介导的增加。此外，一氧化氮刺激的黏着斑蛋白和talin表达的增加通过蛋白激酶G依赖性途径发生，因此与先前一氧化氮调节转录的其他机制不同。黏着斑蛋白mRNA在机械刺激的肌纤维中的分布分析表明，该mRNA高度集中在肌腱连接处，这支持了以下假设：肌腱连接处是不同的结构域，其中细胞骨架蛋白的表达通过一氧化氮和蛋白激酶G依赖性途径由机械刺激来调节。
Mechanical stimuli can cause changes in muscle mass and structure which indicate that mechanisms exist for transducing mechanical stimuli into signals that influence gene expression. Myotendinous junctions show adaptations to modified muscle loading which suggest that these are transcriptionally distinct domains in muscle fibers that may experience local regulation of expression of structural proteins that are concentrated at these sites. Vinculin and talin are cytoskeletal proteins that are highly enriched at myotendinous junctions that we hypothesize to be subject to local transcriptional regulation. Our findings show that mechanical stimulation of muscle cells in vivo and in vitro causes an increase in the expression of vinculin and talin that is mediated by nitric oxide. Furthermore, nitric oxide-stimulated increases in vinculin and talin expression occur through a protein kinase G-dependent pathway and therefore differ from other mechanisms through which nitric oxide has been shown previously to modulate transcription. Analysis of vinculin mRNA distribution in mechanically stimulated muscle fibers shows that the mRNA is highly concentrated at myotendinous junctions, which supports the hypothesis that myotendinous junctions are distinct domains in which the expression of cytoskeletal proteins is modulated by mechanical stimuli through a nitric oxide and protein kinase G-dependent pathway.