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Issue 2, 2018
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Dynamic changes in copper homeostasis and post-transcriptional regulation of Atp7a during myogenic differentiation

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Abstract

Copper (Cu) is an essential metal required for activity of a number of redox active enzymes that participate in critical cellular pathways such as metabolism and cell signaling. Because it is also a toxic metal, Cu must be tightly controlled by a series of transporters and chaperone proteins that regulate Cu homeostasis. The critical nature of Cu is highlighted by the fact that mutations in Cu homeostasis genes cause pathologic conditions such as Menkes and Wilson diseases. While Cu homeostasis in highly affected tissues like the liver and brain is well understood, no study has probed the role of Cu in development of skeletal muscle, another tissue that often shows pathology in these conditions. Here, we found an increase in whole cell Cu content during differentiation of cultured immortalized or primary myoblasts derived from mouse satellite cells. We demonstrate that Cu is required for both proliferation and differentiation of primary myoblasts. We also show that a key Cu homeostasis gene, Atp7a, undergoes dynamic changes in expression during myogenic differentiation. Alternative polyadenylation and stability of Atp7a mRNA fluctuates with differentiation stage of the myoblasts, indicating post-transcriptional regulation of Atp7a that depends on the differentiation state. This is the first report of a requirement for Cu during myogenic differentiation and provides the basis for understanding the network of Cu transport associated with myogenesis.

Graphical abstract: Dynamic changes in copper homeostasis and post-transcriptional regulation of Atp7a during myogenic differentiation

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Publication details

The article was received on 23 Nov 2017, accepted on 04 Jan 2018 and first published on 04 Jan 2018


Article type: Paper
DOI: 10.1039/C7MT00324B
Citation: Metallomics, 2018,10, 309-322
  • Open access: Creative Commons BY license
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    Dynamic changes in copper homeostasis and post-transcriptional regulation of Atp7a during myogenic differentiation

    K. E. Vest, A. L. Paskavitz, J. B. Lee and T. Padilla-Benavides, Metallomics, 2018, 10, 309
    DOI: 10.1039/C7MT00324B

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