The scaffold proteins Tanc1 and Tanc2 are required for myoblast fusion

Abstract Myoblast fusion is a crucial step in myogenesis during embryogenesis and adulthood. In Drosophila , the scaffold protein Antisocial (Ants)/Rols7 plays is essential in myoblast fusion by connecting the cell adhesion surface proteins to the cytoskeleton. Most molecular pathways governing fusion are evolutionary conserved between mammals and flies, but the relative contributions of Tanc1 and Tanc2, mammalian orthologs of Ants/Rols7, in myoblast fusion have not been established. We used the myoblast C2C12 cell line as a model for differentiation and fusion to assess the contributions of Tanc1 and Tanc2 in fusion. We found that Tanc1 and Tanc2 expressions are not modulated during differentiation, but that both proteins are enriched at the cell cortex in proliferating myoblasts. The knockdown of either Tanc1 or Tanc2 in either of the fusing myoblasts impaired fusion. Notably, the expression of human Tanc1 or Tanc2 restored fusion defects observed in Tanc1- or Tanc2-depleted cells. We found that neither Tanc1 nor Tanc2 could substitute for Ants/Rols7 during Drosophila myoblast fusion. We conclude that both Tanc1 and Tanc2 play a role in mammalian myoblast fusion, but there may be some mechanistic differences with the functions of the Drosophila orthologous protein.