title: Lamin A N-terminal phosphorylation is associated with myoblast activation: impairment in Emery-Dreifuss muscular dystrophy.
abstract: BACKGROUND
  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.
  
  
  OBJECTIVE
  To analyse lamin A/C phosphorylation in control and laminopathic muscle cells.
  
  
  METHODS
  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.
  
  
  RESULTS
  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.
  
  
  CONCLUSIONS
  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.
authors.affiliation: ITOI, CNR, Unit of Bologna, c/o IOR, Bologna, Italy.
authors.forename: V
authors.initials: V
authors.lastname: Cenni
authors.forename: P
authors.initials: P
authors.lastname: Sabatelli
authors.forename: E
authors.initials: E
authors.lastname: Mattioli
authors.forename: S
authors.initials: S
authors.lastname: Marmiroli
authors.forename: C
authors.initials: C
authors.lastname: Capanni
authors.forename: A
authors.initials: A
authors.lastname: Ognibene
authors.forename: S
authors.initials: S
authors.lastname: Squarzoni
authors.forename: N M
authors.initials: NM
authors.lastname: Maraldi
authors.forename: G
authors.initials: G
authors.lastname: Bonne
authors.forename: M
authors.initials: M
authors.lastname: Columbaro
authors.forename: L
authors.initials: L
authors.lastname: Merlini
authors.forename: G
authors.initials: G
authors.lastname: Lattanzi
mesh_terms: D000818:Animals; D002454:Cell Differentiation; D002460:Cell Line; D006801:Humans; D007328:Insulin / Q000378:metabolism; D034904:Lamin Type A / Q000235:genetics / Q000378:metabolism*; D051379:Mice; D018485:Muscle Fibers, Skeletal / Q000378:metabolism; D049288:Muscular Dystrophies, Limb-Girdle / Q000235:genetics / Q000378:metabolism / Q000473:pathology; D020389:Muscular Dystrophy, Emery-Dreifuss / Q000235:genetics / Q000378:metabolism*; D032446:Myoblasts / Q000378:metabolism*; D010766:Phosphorylation; D011499:Protein Processing, Post-Translational; D015398:Signal Transduction
chemical_list: D007328:Insulin; C494847:LMNA protein, human; D034904:Lamin Type A
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