POSITIONING OF CELL NUCLEUS IN THE PERIPHERY OF SKELETAL MYOFIBERS

Orateur : Edgar GOMES (Université Lisbonne, Portugal)

Nuclear movements are important for multiple cellular functions. During skeletal myofiber formation or regeneration, nuclei move from the center to the periphery of the myofiber for proper muscle function. In different muscle disorders centrally located nuclei are found. Using theoretical and experimental approaches, we demonstrate that nuclear movement to the periphery of myofibers is mediated by centripetal forces around the nucleus generated by myofibrils to squeeze the nucleus to the periphery of myofibers. These forces arise from myofibril contraction and cross-linking 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 cross-link myofibrils for nuclear movement. We finally show that peripheral nuclear positioning is triggered by local accumulation of fibronectin secreted by myofibroblasts. These discoveries can pave the way to novel therapeutic strategies for muscle disorders.

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