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Normal cultured myoblasts exhibit a highly organized cytoskeletal framework, which gives them a fusiform shape, and numerous myofilaments, as well as desmosomes, intercellular junctions and a large network of neurites. The highly organized cytoskeletal framework, which is typical of this cell type, is maintained throughout myoblast differentiation and it appears that myotube formation is dependent upon the presence of specific proteins (myoD and myf5) in the nucleus. An additional protein, Hsp70, is also required for myoblast fusion, since the latter is blocked in these cells by heat-shock. Myotube formation is also inhibited in the presence of dinitrophenol, an uncoupler of oxidative phosphorylation, and in the presence of antimycin A, an inhibitor of electron transport. The two latter effects can be reversed by the addition of glucose and acetate, indicating that a major source of energy required for fusion is oxidative phosphorylation. 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