When Two Become One: How Novel Fusion Proteins Build Myocytes

Published September 2018 | Developmental Cell

Understanding how developing myoblasts fuse to form functional muscle cells is critical to learning about normal muscle development, regeneration and growth, and for studying diseases of muscle tissue.

Doug Millay, PhD, and colleagues set out to understand the mechanisms of cell fusion driven by the proteins myomaker and myomerger, which they discovered in previous work.

This study reveals that each protein controls different steps of the fusion process. Myomaker is involved in hemifusion, where the outer layer of the cells stick together and mix. Myomerger completes fusion by forming pores that allow the contents of cells to blend. These mechanisms are very different from those followed by traditional fusion proteins.

“This study is fundamentally defining a new way in which cells and cell membranes can fuse,” Millay says. “These findings open up possibilities for how mammalian cells could accomplish fusion, not only for muscle cells, but for all the other cell types that fuse.”

In the long-term future, Millay says it may be possible to use the membrane activities of myomaker and myomerger to improve delivery of therapeutic material to skeletal muscle.

The two-step mechanism revealed in this study was unexpected, which further illustrates that “you can’t predict where fundamental research might take you,” Millay says.