Roman William, Martins João P, Carvalho Filomena A, Voituriez Raphael, Abella Jasmine V G, Santos Nuno C, Cadot Bruno, Way Michael, Gomes Edgar R
Sorbonne Universités, UPMC Univ Paris 06, INSERM UMRS974, CNRS FRE3617, Center for Research in Myology, GH Pitié-Salpêtrière, 47 Boulevard de l'Hôpital, 75013 Paris, France.
Centre de Référence de Pathologie Neuromusculaire Paris-Est, Institut de Myologie, GHU La Pitié-Salpêtrière, Assistance Publique-Hôpitaux de Paris, 75013 Paris, France.
Nat Cell Biol. 2017 Oct;19(10):1189-1201. doi: 10.1038/ncb3605. Epub 2017 Sep 11.
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.
核运动对多种细胞功能至关重要，且由运动蛋白和细胞骨架产生的极化力驱动。在骨骼肌纤维形成或再生过程中，细胞核从肌纤维中心移至外周以实现正常肌肉功能。位于中心的细胞核也见于不同的肌肉疾病中。通过理论和实验方法，我们证明细胞核向肌纤维外周的移动是由细胞核周围的向心力量介导的。这些力量源于肌原纤维收缩和交联，它们围绕细胞核“咬合”，同时由核纤层蛋白A/C对核硬度进行严格调控。此外，含有Arpc5L的Arp2/3复合物与γ-肌动蛋白共同作用，以组织结蛋白交联肌原纤维从而实现核运动。我们的研究表明，肌原纤维施加的向心力量将细胞核挤压至肌纤维外周。
