Myofibril contraction and crosslinking drive nuclear movement to the periphery of skeletal muscle
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William Roman João P Martins Filomena A Carvalho Raphael Voituriez Jasmine VG Abella Nuno C Santos Bruno Cadot Michael Way Edgar R GomesAbstract
Nuclear movements are important for multiple cellular functions, and are driven by polarized forces generated by motor proteins and the cytoskeleton. During skeletal myofibre formation or regeneration, nuclei move from the centre to the periphery of the myofibre for proper muscle function. Centrally located nuclei are also found in different muscle disorders. Using theoretical and experimental approaches, we demonstrate that nuclear movement to the periphery of myofibres is mediated by centripetal forces around the nucleus. These forces arise from myofibril contraction and crosslinking that 'zip' around the nucleus in combination with tight regulation of nuclear stiffness by lamin A/C. In addition, an Arp2/3 complex containing Arpc5L together with γ-actin is required to organize desmin to crosslink myofibrils for nuclear movement. Our work reveals that centripetal forces exerted by myofibrils squeeze the nucleus to the periphery of myofibres.
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Journal Nature Cell Biology
Volume 19
Issue number 10
Pages 1189-1201
Available online
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Publisher website (DOI) 10.1038/ncb3605
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Europe PubMed Central 28892082
Pubmed 28892082
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