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Nuclear movement to the periphery of skeletal muscle cells
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Resumo(s)
Nuclear movements are important for multiple cellular functions and are driven by polarized forces generated by motor proteins and cytoskeleton. During skeletal muscle development and regeneration, nuclei move from the center to the periphery of the myofiber. Moreover, nuclear movement to the periphery begins with the emergence of a nuclear wrinkle between myofibrils that gradually increases forming a bud. The nucleus undergoes severe deformations while being squeezed by myofibrils until it is finally expelled to the periphery. Nuclear positioning at the periphery of myofibers is crucial for proper muscle function, with centrally located nuclei being linked to several muscle disorders. Here we demonstrate that nuclear movement to the periphery of myofibers is dependent on local changes in nuclear stiffness regulated by Lamin A/C. Furthermore, we found that this movement is mediated by Desmin dependent myofibril crosslinking and zipping, while Plectin, Arpc5L and γ actin are necessary for proper Desmin organization at the z-lines. Finally, Nesprin1 depletion resulted in a severe decrease of peripheral nuclei which suggests that it might play a role in nuclear movement to the periphery possibly associated with mechanotransduction.
Descrição
Palavras-chave
Myofiber Nuclear movement to the periphery Nuclear stiffness Myofibril crosslinking Lamin A/C Desmin