Nuclear envelope rupture is induced by actin-based nucleus confinement

J Cell Biol. 2016 Oct 10;215(1):27-36. doi: 10.1083/jcb.201603053. Epub 2016 Oct 3.


Repeated rounds of nuclear envelope (NE) rupture and repair have been observed in laminopathy and cancer cells and result in intermittent loss of nucleus compartmentalization. Currently, the causes of NE rupture are unclear. Here, we show that NE rupture in cancer cells relies on the assembly of contractile actin bundles that interact with the nucleus via the linker of nucleoskeleton and cytoskeleton (LINC) complex. We found that the loss of actin bundles or the LINC complex did not rescue nuclear lamina defects, a previously identified determinant of nuclear membrane stability, but did decrease the number and size of chromatin hernias. Finally, NE rupture inhibition could be rescued in cells treated with actin-depolymerizing drugs by mechanically constraining nucleus height. These data suggest a model of NE rupture where weak membrane areas, caused by defects in lamina organization, rupture because of an increase in intranuclear pressure from actin-based nucleus confinement.

MeSH terms

  • Actins / metabolism*
  • Cell Line, Tumor
  • Chromatin / metabolism
  • Cytochalasin D / pharmacology
  • Heterocyclic Compounds, 4 or More Rings / pharmacology
  • Humans
  • Multiprotein Complexes / metabolism
  • Nuclear Envelope / drug effects
  • Nuclear Envelope / metabolism*
  • Stress, Mechanical
  • Time-Lapse Imaging


  • Actins
  • Chromatin
  • Heterocyclic Compounds, 4 or More Rings
  • Multiprotein Complexes
  • blebbistatin
  • Cytochalasin D

Associated data

  • RefSeq/NM_005573