The prelamin A pre-peptide induces cardiac and skeletal myoblast differentiation.
Prelamin A processing is unique amongst mammalian proteins and results in the production of a farnesylated and carboxymethylated peptide. We examined the effect of pathogenic LMNA mutations on prelamin A processing, and of the covalently modified peptide on cardiac and skeletal myoblast differentiation. Here we report a mutation associated with dilated cardiomyopathy prevents prelamin A peptide production. In addition, topical application of the covalently modified C-terminal peptide to proliferating skeletal and cardiac myoblasts induced myotube and striated tissue formation, respectively. Western blot analysis revealed that skeletal and cardiac myoblasts are the first cell lines examined to contain unprocessed prelamin A, and immunostaining of peptide-treated cells revealed a previously unidentified role for prelamin A in cytoskeleton formation and intercellular organization. These results demonstrate a direct role for prelamin A in myoblast differentiation and indicate the prelamin A peptide may have therapeutic potential.
Brodsky
Gary L
GL
Division of Medical Oncology, Department of Medicine, University of Colorado at Denver and Health Sciences Center, Denver, CO 80262, USA. Gary.Brodsky@uchsc.edu
Bowersox
Jeffrey A
JA
Fitzgerald-Miller
Lisa
L
Miller
Leslie A
LA
Maclean
Kenneth N
KN
D000818:Animals; D002454:Cell Differentiation; D002460:Cell Line; D034904:Lamin Type A; D051379:Mice; D018485:Muscle Fibers, Skeletal / Q000166:cytology* / Q000378:metabolism*; D016297:Mutagenesis, Site-Directed; D032446:Myoblasts / Q000166:cytology* / Q000378:metabolism*; D032383:Myocytes, Cardiac / Q000166:cytology* / Q000378:metabolism*; D009687:Nuclear Proteins / Q000235:genetics / Q000378:metabolism*; D011498:Protein Precursors / Q000235:genetics / Q000378:metabolism*; D013329:Structure-Activity Relationship
D034904:Lamin Type A; D009687:Nuclear Proteins; D011498:Protein Precursors; C090764:prelamin A