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PMID: 15744034 Published · ppublish English Journal Article Research Support, Non-U.S. Gov't

Lamin A N-terminal phosphorylation is associated with myoblast activation: impairment in Emery-Dreifuss muscular dystrophy.

Journal of medical genetics ·Vol. 42 ·No. 3 ·2005-03-00 ·Pages 214-20

Cenni V, Sabatelli P, Mattioli E, Marmiroli S, Capanni C, Ognibene A, Squarzoni S, Maraldi NM, Bonne G, Columbaro M, Merlini L, Lattanzi G

Abstract

Skeletal muscle disorders associated with mutations of lamin A/C gene include autosomal Emery-Dreifuss muscular dystrophy and limb girdle muscular dystrophy 1B. The pathogenic mechanism underlying these diseases is unknown. Recent data suggest an impairment of signalling mechanisms as a possible cause of muscle malfunction. A molecular complex in muscle cells formed by lamin A/C, emerin, and nuclear actin has been identified. The stability of this protein complex appears to be related to phosphorylation mechanisms. To analyse lamin A/C phosphorylation in control and laminopathic muscle cells. Lamin A/C N-terminal phosphorylation was determined in cultured mouse myoblasts using a specific antibody. Insulin treatment of serum starved myoblast cultures was carried out to evaluate involvement of insulin signalling in the phosphorylation pathway. Screening of four Emery-Dreifuss and one limb girdle muscular dystrophy 1B cases was undertaken to investigate lamin A/C phosphorylation in both cultured myoblasts and mature muscle fibres. Phosphorylation of lamin A was observed during myoblast differentiation or proliferation, along with reduced lamin A/C phosphorylation in quiescent myoblasts. Lamin A N-terminus phosphorylation was induced by an insulin stimulus, which conversely did not affect lamin C phosphorylation. Lamin A/C was also hyperphosphorylated in mature muscle, mostly in regenerating fibres. Lamin A/C phosphorylation was strikingly reduced in laminopathic myoblasts and muscle fibres, while it was preserved in interstitial fibroblasts. Altered lamin A/C interplay with a muscle specific phosphorylation partner might be involved in the pathogenic mechanism of Emery-Dreifuss muscular dystrophy and limb girdle muscular dystrophy 1B.

MeSH Terms
Animals Cell Differentiation Cell Line Humans Insulin/metabolism Lamin Type A/genetics,metabolism Mice Muscle Fibers, Skeletal/metabolism Muscular Dystrophies, Limb-Girdle/genetics,metabolism,pathology Muscular Dystrophy, Emery-Dreifuss/genetics,metabolism Myoblasts/metabolism Phosphorylation Protein Processing, Post-Translational Signal Transduction
Chemicals
Insulin LMNA protein, human Lamin Type A
Authors & Affiliations
12 authors, click to expand affiliations / ORCID
Cenni V
ITOI, CNR, Unit of Bologna, c/o IOR, Bologna, Italy.
Sabatelli P
Mattioli E
Marmiroli S
Capanni C
Ognibene A
Squarzoni S
Maraldi N M
Bonne G
Columbaro M
Merlini L
Lattanzi G
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Article Info
Journal
Journal of medical genetics
Abbr.
J Med Genet
ISSN
1468-6244
DOI
10.1136/jmg.2004.026112
Published
2005-03-00
Pages
214-20
Language
English
Region
England
NLM ID
2985087R
PMCID
PMC1736020
Subset
IM
External Links
PubMed source DOI: 10.1136/jmg.2004.026112 PMC Full Text View journal details
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