title: Participation of myosin Va and Pka type I in the regeneration of neuromuscular junctions.
abstract: BACKGROUND
  The unconventional motor protein, myosin Va, is crucial for the development of the mouse neuromuscular junction (NMJ) in the early postnatal phase. Furthermore, the cooperative action of protein kinase A (PKA) and myosin Va is essential to maintain the adult NMJ. We here assessed the involvement of myosin Va and PKA in NMJ recovery during muscle regeneration.
  
  
  RESULTS
  To address a putative role of myosin Va and PKA in the process of muscle regeneration, we used two experimental models the dystrophic mdx mouse and Notexin-induced muscle degeneration/regeneration. We found that in both systems myosin Va and PKA type I accumulate beneath the NMJs in a fiber maturation-dependent manner. Morphologically intact NMJs were found to express stable nicotinic acetylcholine receptors and to accumulate myosin Va and PKA type I in the subsynaptic region. Subsynaptic cAMP signaling was strongly altered in dystrophic muscle, particularly in fibers with severely subverted NMJ morphology.
  
  
  CONCLUSIONS
  Our data show a correlation between the subsynaptic accumulation of myosin Va and PKA type I on the one hand and NMJ regeneration status and morphology, AChR stability and specificity of subsynaptic cAMP handling on the other hand. This suggests an important role of myosin Va and PKA type I for the maturation of NMJs in regenerating muscle.
authors: Institut für Toxikologie und Genetik, Karlsruhe Institute of Technology, Eggenstein-Leopoldshafen, Germany.
authors: Ira Verena
authors: IV
authors: Röder
authors: Siegfried
authors: S
authors: Strack
authors: Markus
authors: M
authors: Reischl
authors: Oliver
authors: O
authors: Dahley
authors: Muzamil Majid
authors: MM
authors: Khan
authors: Olivier
authors: O
authors: Kassel
authors: Manuela
authors: M
authors: Zaccolo
authors: Rüdiger
authors: R
authors: Rudolf
mesh_terms: D000818:Animals; D015740:Calcitonin Gene-Related Peptide / Q000378:metabolism; D000242:Cyclic AMP / Q000378:metabolism; D054743:Cyclic AMP-Dependent Protein Kinase Type I / Q000378:metabolism*; D004546:Elapid Venoms / Q000494:pharmacology; D051379:Mice; D008810:Mice, Inbred C57BL; D018101:Mice, Inbred mdx; D018482:Muscle, Skeletal / Q000187:drug effects / Q000201:enzymology / Q000473:pathology / Q000503:physiopathology; D009137:Muscular Dystrophy, Animal / Q000473:pathology; D018995:Myosin Heavy Chains / Q000378:metabolism*; D024701:Myosin Type V / Q000378:metabolism*; D009469:Neuromuscular Junction / Q000187:drug effects / Q000201:enzymology* / Q000473:pathology / Q000503:physiopathology*; D055550:Protein Stability / Q000187:drug effects; D011950:Receptors, Cholinergic / Q000378:metabolism; D012038:Regeneration / Q000187:drug effects; D015398:Signal Transduction / Q000187:drug effects; D013569:Synapses / Q000187:drug effects / Q000378:metabolism / Q000473:pathology
chemical_list: D004546:Elapid Venoms; C513082:Myo5a protein, mouse; D011950:Receptors, Cholinergic; C005082:notexin; D000242:Cyclic AMP; D054743:Cyclic AMP-Dependent Protein Kinase Type I; D024701:Myosin Type V; D018995:Myosin Heavy Chains; D015740:Calcitonin Gene-Related Peptide