Myofibril contraction and crosslinking drive nuclear movement to the periphery of skeletal muscle

Nat Cell Biol. 2017 Oct;19(10):1189-1201. doi: 10.1038/ncb3605. Epub 2017 Sep 11.

Abstract

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.

Publication types

  • Video-Audio Media

MeSH terms

  • Actin-Related Protein 2-3 Complex / genetics
  • Actin-Related Protein 2-3 Complex / metabolism
  • Actins / genetics
  • Actins / metabolism
  • Animals
  • Animals, Newborn
  • Cell Nucleus / physiology*
  • Cells, Cultured
  • Lamin Type A / genetics
  • Lamin Type A / metabolism
  • Mice, Inbred C57BL
  • Microscopy, Fluorescence
  • Microscopy, Video
  • Models, Biological
  • Movement*
  • Muscle Contraction*
  • Muscle, Skeletal / physiology*
  • Myofibrils / physiology*
  • RNA Interference
  • Time Factors
  • Time-Lapse Imaging
  • Transfection

Substances

  • Actin-Related Protein 2-3 Complex
  • Actins
  • Arpc5 protein, mouse
  • Lamin Type A
  • Lmna protein, mouse