The R482Q lamin A/C mutation that causes lipodystrophy does not prevent nuclear targeting of lamin A in adipocytes or its interaction with emerin

Eur J Hum Genet. 2001 Mar;9(3):204-8. doi: 10.1038/sj.ejhg.5200609.

Abstract

Most pathogenic missense mutations in the lamin A/C gene identified so far cause autosomal-dominant dilated cardiomyopathy and/or Emery-Dreifuss muscular dystrophy. A few specific mutations, however, cause a disease with remarkably different clinical features: FPLD, or familial partial lipodystrophy (Dunnigan-type), which mainly affects adipose tissue. We have prepared lamin A with a known FPLD mutation (R482Q) by in vitro mutagenesis. Nuclear targeting of lamin A in transfected COS cells, human skeletal muscle cells or mouse adipocyte cell cultures (pre- and post-differentiation) was not detectably affected by the mutation. Quantitative in vitro measurements of lamin A interaction with emerin using a biosensor also showed no effect of the mutation. The results show that the loss of function of R482 in lamin A/C in FPLD does not involve loss of ability to form a nuclear lamina or to interact with the nuclear membrane protein, emerin.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Adipocytes / metabolism*
  • Animals
  • Base Sequence
  • COS Cells
  • Cardiomyopathy, Dilated / genetics
  • Cell Nucleus / metabolism*
  • DNA Primers
  • Lamin Type A
  • Lamins
  • Lipodystrophy / genetics*
  • Membrane Proteins / metabolism*
  • Muscular Dystrophies / genetics
  • Mutation*
  • Nuclear Proteins / genetics*
  • Nuclear Proteins / metabolism
  • Thymopoietins / metabolism*

Substances

  • DNA Primers
  • Lamin Type A
  • Lamins
  • Membrane Proteins
  • Nuclear Proteins
  • Thymopoietins
  • emerin