Specific contribution of lamin A and lamin C in the development of laminopathies

Exp Cell Res. 2008 Aug 1;314(13):2362-75. doi: 10.1016/j.yexcr.2008.04.017. Epub 2008 May 10.


Mutations in the lamin A/C gene are involved in multiple human disorders for which the pathophysiological mechanisms are partially understood. Conflicting results prevail regarding the organization of lamin A and C mutants within the nuclear envelope (NE) and on the interactions of each lamin to its counterpart. We over-expressed various lamin A and C mutants both independently and together in COS7 cells. When expressed alone, lamin A with cardiac/muscular disorder mutations forms abnormal aggregates inside the NE and not inside the nucleoplasm. Conversely, the equivalent lamin C organizes as intranucleoplasmic aggregates that never connect to the NE as opposed to wild type lamin C. Interestingly, the lamin C molecules present within these aggregates exhibit an abnormal increased mobility. When co-expressed, the complex formed by lamin A/C aggregates in the NE. Lamin A and C mutants for lipodystrophy behave similarly to the wild type. These findings reveal that lamins A and C may be differentially affected depending on the mutation. This results in multiple possible physiological consequences which likely contribute in the phenotypic variability of laminopathies. The inability of lamin C mutants to join the nuclear rim in the absence of lamin A is a potential pathophysiological mechanism for laminopathies.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Animals
  • COS Cells
  • Cell Nucleus / metabolism
  • Chemical Precipitation
  • Chlorocebus aethiops
  • Disease Progression
  • Genetic Diseases, Inborn / etiology*
  • Genetic Diseases, Inborn / genetics
  • Genetic Diseases, Inborn / metabolism
  • Humans
  • Lamin Type A / genetics
  • Lamin Type A / metabolism
  • Lamin Type A / physiology*
  • Muscular Dystrophy, Emery-Dreifuss / genetics
  • Muscular Dystrophy, Emery-Dreifuss / metabolism
  • Nuclear Envelope / metabolism
  • Point Mutation
  • Protein Binding
  • Protein Transport
  • Transfection


  • Lamin Type A
  • lamin C