Myoblast fusion is a fundamental process necessary for muscle formation during development and regeneration ( 1). These data reveal that myoblast fusion requires myomaker activity at the plasma membrane and is potentially regulated by proper myomaker trafficking. Indeed, C-terminal mutagenesis analysis highlighted the importance of a C-terminal leucine for function. Moreover, dissection of the C terminus revealed that palmitoylation was not sufficient for complete fusogenic activity suggesting a function for other amino acids within this C-terminal region. Trafficking of myomaker is regulated by palmitoylation of C-terminal cysteine residues that allows Golgi localization. Using a synchronized fusion assay, we demonstrated that myomaker functions at the plasma membrane to drive fusion. These results raised questions regarding the precise cellular location of myomaker function and mechanisms that govern myomaker trafficking between these cellular compartments. Two independent antibodies showed that whereas myomaker does localize to the plasma membrane in cultured myoblasts, the protein also resides in the Golgi and post-Golgi vesicles. To explore these questions, we first examined the cellular localization of endogenous myomaker. However, the specific function of myomaker and how its function is regulated are unknown. Previous studies identified myomaker (Tmem8c) as a muscle-specific membrane protein essential for fusion. Multinucleated skeletal muscle fibers form through the fusion of myoblasts during development and regeneration.
0 kommentar(er)
