title: Multiple novel functions of lamina associated polypeptide 2α in striated muscle.
abstract: Lamina-associated polypeptide 2α (LAP2α) is a nucleoplasmic protein that interacts with A-type lamins and the retinoblastoma protein (pRb) and affects pRb-mediated cell cycle regulation and chromatin organization. Mutations in lamin A/C and LAP2α cause late onset striated muscle diseases, but the molecular mechanisms are poorly understood. We have recently reported on the striated muscle phenotype of LAP2α-deficient mice, revealing new unexpected roles of LAP2α. Loss of LAP2α in skeletal muscle caused an upregulated stem cell-type gene expression in muscle satellite cell progeny and their delayed myogenic differentiation in vitro. In vivo, the myofiber-associated muscle stem cell pool was increased. In addition, absence of LAP2α promoted muscle remodeling towards fast myofiber types in the soleus muscle of old animals. In cardiac tissue, deletion of LAP2α caused systolic dysfunction in young mice with an increased susceptibility for fibrosis in old animals. The functional impairment in the heart was accompanied by a deregulation of major cardiac transcription factors, GATA4 and MEF2c and activation of compensatory pathways, including the downregulation of β-adrenergic receptor signaling.Here we discuss potential functions of LAP2α in striated muscle at molecular level and how loss of these functions may cause the diverse muscle phenotypes. We propose that LAP2α serves as a transcriptional co-regulator, which controls muscle specific gene expression during muscle regeneration, muscle remodeling and stress response.
authors.affiliation: Department of Medical Biochemistry, Max F. Perutz Laboratories, Medical University of Vienna, Vienna, Austria.
authors.forename: Ivana
authors.initials: I
authors.lastname: Gotic
authors.forename: Roland
authors.initials: R
authors.lastname: Foisner
mesh_terms: D000375:Aging; D000818:Animals; D004268:DNA-Binding Proteins / Q000172:deficiency / Q000235:genetics*; D050991:GATA4 Transcription Factor / Q000235:genetics / Q000378:metabolism; D005786:Gene Expression Regulation / Q000502:physiology*; D064326:MEF2 Transcription Factors; D008565:Membrane Proteins / Q000172:deficiency / Q000235:genetics*; D051379:Mice; D018345:Mice, Knockout; D018482:Muscle, Skeletal / Q000502:physiology*; D009206:Myocardium / Q000378:metabolism*; D018006:Myogenic Regulatory Factors / Q000235:genetics / Q000378:metabolism; D012038:Regeneration; D015398:Signal Transduction / Q000502:physiology; D013312:Stress, Physiological; D018487:Ventricular Dysfunction, Left / Q000378:metabolism / Q000503:physiopathology
chemical_list: D004268:DNA-Binding Proteins; D050991:GATA4 Transcription Factor; C484171:Gata4 protein, mouse; D064326:MEF2 Transcription Factors; C578041:Mef2c protein, mouse; D008565:Membrane Proteins; D018006:Myogenic Regulatory Factors; C093413:lamina-associated polypeptide 2