FSHD Myotubes with Different Phenotypes Exhibit Distinct Proteomes

摘要: Facioscapulohumeral muscular dystrophy (FSHD) is a progressive muscle disorder linked to contraction of the D4Z4 repeat array in 4q35 subtelomeric region. This deletion induces epigenetic modifications that affect expression several genes located vicinity. In each element, we identified double homeobox 4 (DUX4) gene. DUX4 expresses transcription factor plays major role development FSHD through initiation large gene dysregulation cascade causes myogenic differentiation defects, atrophy and reduced response oxidative stress. Because miRNAs variably mRNA expression, proteomic approaches are required define dysregulated pathways FSHD. this study, optimized differential isotope protein labeling (ICPL) method combined with shotgun analysis using gel-free system (2DLC-MS/MS) study myotubes. Primary CD56+ myoblasts were found fuse into myotubes presenting various proportions an atrophic or disorganized phenotype. To better understand defect, our improved procedure was used compare predominantly same matching healthy control. presented decreased structural contractile components. phenotype suggests occurrence atrophy-associated proteolysis likely results from DUX4-mediated cascade. The skeletal myosin isoforms while non-muscle complexes more abundant. myotubes, not reduced, increased proteins mostly involved microtubule network organization myofibrillar remodeling. A common feature both myotube phenotypes disturbance caveolar proteins, such as PTRF MURC. Taken together, data suggest changes trafficking membrane microdomains Finally, adjustment nuclear fractionation compatible mass spectrometry allowed us highlight alterations processing stability.