Specific phosphorylation of Ser458 of A-type lamins in LMNA-associated myopathy patients.
J Cell Sci
; 123(Pt 22): 3893-900, 2010 Nov 15.
Article
in En
| MEDLINE
| ID: mdl-20980393
ABSTRACT
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.
Full text:
1
Database:
MEDLINE
Main subject:
Lamin Type A
/
Muscular Dystrophies
Type of study:
Risk_factors_studies
/
Screening_studies
Limits:
Adult
/
Animals
/
Child
/
Child, preschool
/
Female
/
Humans
/
Male
/
Middle aged
Language:
En
Journal:
J Cell Sci
Year:
2010
Type:
Article
Affiliation country:
Japan