Cu (Cu) is essential for several biochemical pathways due to its role as a catalytic cofactor or allosteric regulator of enzymes. Its import and distribution are tightly controlled by transporters and metallochaperones and Cu homeostasis is maintained by balancing Cu uptake and export. Genetic diseases are caused by impaired Cu transporters CTR1, ATP7A, or ATP7B but little is known about the regulatory mechanisms by which these proteins meet the fluctuating demands of Cu in specific tissues. Cu is required for differentiation of skeletal myoblasts to myotubes. Here, we demonstrate that ATP7A is needed for myotube formation and that its increased abundance during differentiation is mediated by stabilization of Atp7a mRNA via the 3' untranslated region. Increased ATP7A levels during differentiation resulted in increased Cu delivery to lysyl oxidase, a secreted cuproenzyme that needed for myotube formation. These studies identify a previously unknown role for Cu in regulating muscle differentiation and have broad implications for understanding Cu-dependent differentiation in other tissues.

中文翻译：

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Atp7a RNA 的调节有助于骨骼肌细胞中分化依赖性铜的重新分配。

Cu (Cu) 由于其作为酶的催化辅助因子或变构调节剂的作用，对于多种生化途径至关重要。它的输入和分配受到转运蛋白和金属伴侣的严格控制，并且通过平衡铜的吸收和输出来维持铜的稳态。遗传性疾病是由铜转运蛋白 CTR1、ATP7A 或 ATP7B 受损引起的，但人们对这些蛋白质满足特定组织中铜波动需求的调节机制知之甚少。骨骼肌成肌细胞分化为肌管需要铜。在这里，我们证明 ATP7A 是肌管形成所必需的，并且分化过程中 ATP7A 丰度的增加是通过 3' 非翻译区稳定 Atp7a mRNA 介导的。分化过程中 ATP7A 水平的增加导致向赖氨酰氧化酶（一种肌管形成所需的分泌性铜酶）的铜输送量增加。这些研究确定了铜在调节肌肉分化中的先前未知的作用，并且对于理解其他组织中铜依赖性分化具有广泛的意义。