Broken Nuclei--Lamins, Nuclear Mechanics, and Disease

Trends Cell Biol. 2014 Apr;24(4):247-56. doi: 10.1016/j.tcb.2013.11.004. Epub 2013 Dec 2.

Abstract

Mutations in lamins, which are ubiquitous nuclear intermediate filaments, lead to a variety of disorders including muscular dystrophy and dilated cardiomyopathy. Lamins provide nuclear stability, help connect the nucleus to the cytoskeleton, and can modulate chromatin organization and gene expression. Nonetheless, the diverse functions of lamins remain incompletely understood. We focus here on the role of lamins on nuclear mechanics and their involvement in human diseases. Recent findings suggest that lamin mutations can decrease nuclear stability, increase nuclear fragility, and disturb mechanotransduction signaling, possibly explaining the muscle-specific defects in many laminopathies. At the same time, altered lamin expression has been reported in many cancers, where the resulting increased nuclear deformability could enhance the ability of cells to transit tight interstitial spaces, thereby promoting metastasis.

Keywords: cell mechanics; cytoskeleton; gene regulation; laminopathy; protein assembly/structure.

Publication types

  • Research Support, N.I.H., Extramural
  • Research Support, Non-U.S. Gov't
  • Research Support, U.S. Gov't, Non-P.H.S.
  • Review

MeSH terms

  • Animals
  • Cell Nucleus / metabolism*
  • Cytoskeleton / metabolism*
  • Gene Expression Regulation
  • Humans
  • Lamins / genetics*
  • Mechanotransduction, Cellular
  • Mutation / genetics

Substances

  • Lamins