Study of the role of Axl, an engulfment receptor, in myoblast fusion

Abstract

Myogenesis, the fusion of myoblasts into multinucleated myotubes, plays a vital role in regeneration after injury and during development. Phosphatidylserine (PS), a phospholipid constituent of cell membranes, is recognized as an ‘eat-me’ signal during phagocytosis of apoptotic cells. PS is also known to be involved in various fusion processes such as the fertilization of a sperm and an egg, generation of multinucleated osteoclasts, and fusion of macrophages. It has been known that not only PS blocking but also impairment of its receptors compromise myotube formation. Axl, a member of the TAM family of PS receptors, is known for its involvement in efferocytosis, tumor growth, metastasis, angiogenesis, and cell migration during development. However, the role of Axl in myoblast fusion remains elusive. Here, I show that Axl functions as a receptor indirectly recognizing PS exposed on C2C12 cells, facilitating myoblast fusion. Axl exhibited the highest mRNA expression among various engulfment receptors in C2C12 myoblasts and an increase in Axl expression was observed during myoblast fusion. In addition, depletion of Axl or blocking of PS recognition by Axl also diminished the efficiency of myoblast fusion. These findings suggest that Axl plays an important role in myoblast fusion and PS recognition by Axl is required for the process.