Failure of lamin A/C to functionally assemble in R482L mutated familial partial lipodystrophy fibroblasts: altered intermolecular interaction with emerin and implications for gene transcription

Exp Cell Res. 2003 Nov 15;291(1):122-34. doi: 10.1016/s0014-4827(03)00395-1.


Familial partial lipodystrophy is an autosomal dominant disease caused by mutations of the LMNA gene encoding alternatively spliced lamins A and C. Abnormal distribution of body fat and insulin resistance characterize the clinical phenotype. In this study, we analyzed primary fibroblast cultures from a patient carrying an R482L lamin A/C mutation by a morphological and biochemical approach. Abnormalities were observed consisting of nuclear lamin A/C aggregates mostly localized close to the nuclear lamina. These aggregates were not bound to either DNA-containing structures or RNA splicing intranuclear compartments. In addition, emerin did not colocalize with nuclear lamin A/C aggregates. Interestingly, emerin failed to interact with lamin A in R482L mutated fibroblasts in vivo, while the interaction with lamin C was preserved in vitro, as determined by coimmunoprecipitation experiments. The presence of lamin A/C nuclear aggregates was restricted to actively transcribing cells, and it was increased in insulin-treated fibroblasts. In fibroblasts carrying lamin A/C nuclear aggregates, a reduced incorporation of bromouridine was observed, demonstrating that mutated lamin A/C in FPLD cells interferes with RNA transcription.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Alternative Splicing / genetics
  • Cells, Cultured
  • Fibroblasts / metabolism*
  • Fibroblasts / pathology
  • Fibroblasts / ultrastructure
  • Heterochromatin / genetics
  • Heterochromatin / pathology
  • Heterochromatin / ultrastructure
  • Humans
  • Insulin / pharmacology
  • Interphase / genetics
  • Lamin Type A / genetics
  • Lamin Type A / metabolism
  • Lamins / deficiency
  • Lamins / genetics
  • Lamins / metabolism*
  • Lipodystrophy / genetics*
  • Membrane Proteins / metabolism*
  • Microscopy, Electron
  • Mutation / genetics
  • Nuclear Envelope / metabolism
  • Nuclear Envelope / pathology
  • Nuclear Envelope / ultrastructure
  • Nuclear Proteins
  • RNA / biosynthesis
  • RNA / genetics
  • Thymopoietins / metabolism*
  • Transcription, Genetic / drug effects
  • Transcription, Genetic / genetics*


  • Heterochromatin
  • Insulin
  • Lamin Type A
  • Lamins
  • Membrane Proteins
  • Nuclear Proteins
  • Thymopoietins
  • emerin
  • lamin C
  • RNA