Specific phosphorylation of Ser458 of A-type lamins in LMNA-associated myopathy patients

J Cell Sci. 2010 Nov 15;123(Pt 22):3893-900. doi: 10.1242/jcs.072157. Epub 2010 Oct 27.


Mutations in LMNA, which encodes A-type nuclear lamins, cause various human diseases, including myopathy, cardiomyopathy, lipodystrophy and progeria syndrome. To date, little is known about how mutations in a single gene cause a wide variety of diseases. Here, by characterizing an antibody that specifically recognizes the phosphorylation of Ser458 of A-type lamins, we uncover findings that might contribute to our understanding of laminopathies. This antibody only reacts with nuclei in muscle biopsies from myopathy patients with mutations in the Ig-fold motif of A-type lamins. Ser458 phosphorylation is not seen in muscles from control patients or patients with any other neuromuscular diseases. In vitro analysis confirmed that only lamin A mutants associated with myopathy induce phosphorylation of Ser458, whereas lipodystrophy- or progeria-associated mutants do not. We also found that Akt1 directly phosphorylates Ser458 of lamin A with myopathy-related mutations in vitro. These results suggest that Ser458 phosphorylation of A-type lamins correlates with striated muscle laminopathies; this might be useful for the early diagnosis of LMNA-associated myopathies. We propose that disease-specific phosphorylation of A-type lamins by Akt1 contributes to myopathy caused by LMNA mutations.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Adult
  • Animals
  • COS Cells
  • Child
  • Child, Preschool
  • Chlorocebus aethiops
  • Female
  • Humans
  • Immunohistochemistry
  • Lamin Type A / genetics
  • Lamin Type A / metabolism*
  • Male
  • Mice
  • Middle Aged
  • Muscular Dystrophies / genetics
  • Muscular Dystrophies / metabolism*
  • Phosphorylation
  • Transfection


  • LMNA protein, human
  • Lamin Type A