Regulation of Atp7a RNA contributes to differentiation-dependent Cu redistribution in skeletal muscle cells.
Regulation of Atp7a RNA contributes to differentiation-dependent Cu redistribution in skeletal muscle cells.
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ATP7A RNA的调节有助于骨骼肌细胞中分化依赖性的CU重新分布。
DOI：
10.1093/mtomcs/mfad042
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发表时间：
2023-07-10
期刊：
影响因子：
3.4
通讯作者：
Vest, Katherine E.
中科院分区：
文献类型：
--
作者：
Whitlow, Thomas J.;Zhang, Yu;Ferguson, Nathan;Perez, Alexandra M.;Patel, Hemchandra;Link-Kemp, Josephine A.;Larson, Ethan M.;Mezzell, Allison T.;Shanbhag, Vinit C.;Petris, Michael J.;Vest, Katherine E.
由于其作为酶的催化辅助因子或变构调节因子的作用，铜（Cu）在几种生化途径中是必不可少的。铜的输入和分布受到转运体和金属伴侣体的严格控制，铜的吸收和输出平衡维持了铜的体内平衡。遗传性疾病是由铜转运蛋白CTR1、ATP7A或ATP7B受损引起的，但对这些蛋白在特定组织中满足波动的铜需求的调节机制知之甚少。铜是骨骼肌母细胞向肌管分化所必需的。在这里，我们证明了肌管的形成需要ATP7A，分化过程中其丰度的增加是通过3 '非翻译区ATP7A mRNA的稳定介导的。分化过程中ATP7A水平的升高导致赖氨酸氧化酶（肌管形成所需的一种分泌铜原酶）的铜输送增加。这些研究确定了Cu在调节肌肉分化中的未知作用，并对理解其他组织中Cu依赖性分化具有广泛的意义。铜是一种必需但有毒的微量金属营养素，必须保持在一个严密的体内平衡范围内。在这里，我们证明了铜根据骨骼肌母细胞的分化状态被优先用于不同的靶点，并且反式高尔基铜输出蛋白ATP7A的转录后调控有助于铜的再分配。
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. Copper is an essential but toxic trace metal nutrient that must be maintained within a tight homeostatic range. Here, we demonstrate that copper is prioritized to different targets depending on differentiation state in skeletal myoblasts and that post-transcriptional regulation of the trans-Golgi copper exporter ATP7A contributes to copper redistribution.
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DOI：
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发表时间：
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期刊：
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影响因子：
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