title: The R482Q lamin A/C mutation that causes lipodystrophy does not prevent nuclear targeting of lamin A in adipocytes or its interaction with emerin.
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.
authors: MRIC Biochemistry Group, North East Wales Institute, Wrexham, LL11 2AW, UK.
authors: I
authors: I
authors: Holt
authors: L
authors: L
authors: Clements
authors: S
authors: S
authors: Manilal
authors: S C
authors: SC
authors: Brown
authors: G E
authors: GE
authors: Morris
mesh_terms: D017667:Adipocytes / Q000378:metabolism*; D000818:Animals; D001483:Base Sequence; D019556:COS Cells; D002311:Cardiomyopathy, Dilated / Q000235:genetics; D002467:Cell Nucleus / Q000378:metabolism*; D017931:DNA Primers; D034904:Lamin Type A; D034882:Lamins; D008060:Lipodystrophy / Q000235:genetics*; D008565:Membrane Proteins / Q000378:metabolism*; D009136:Muscular Dystrophies / Q000235:genetics; D009154:Mutation; D009687:Nuclear Proteins / Q000235:genetics* / Q000378:metabolism; D013946:Thymopoietins / Q000378:metabolism*
chemical_list: D017931:DNA Primers; D034904:Lamin Type A; D034882:Lamins; D008565:Membrane Proteins; D009687:Nuclear Proteins; D013946:Thymopoietins; C092710:emerin