Two mammalian UNC-45 isoforms are related to distinct cytoskeletal and muscle-specific functions

Previous studies have shown that the UNC-45 protein of C. elegans is required for normal thick filament assembly, binds Hsp90 and the myosin head, and shows molecular chaperone activity. We report here that mice and humans each have two genes that are located on different chromosomes, encode distinct UNC-45-like protein isoforms, and are expressed either in multiple tissues or only in cardiac and skeletal muscles. Their expression is regulated during muscle differentiation in vitro, with the striated muscle isoform mRNA appearing during myoblast fusion. Antisense experiments in C2C12 skeletal myogenic cells demonstrate that decreasing the general cell isoform mRNA reduces proliferation and fusion, while decreasing the striated muscle isoform mRNA affects fusion and sarcomere organization. These results suggest that the general cell UNC-45 isoform may have primarily cytoskeletal functions and that the striated muscle UNC-45 isoform may be restricted to roles in muscle-specific differentiation.