Plectin regulates Wnt signaling mediated-skeletal muscle development by interacting with Dishevelled-2 and...

Skeletal muscle is the most abundant tissue in the human and animal body, loss of its function can lead to muscle aging and various myogenic diseases. The skeletal muscle development is a complex and tightly regulated process, which is driven by a variety of many factors, signaling pathways and regulatory mechanisms. Plectin (Plec), a cytolinker protein, is ubiquitously expressed in various tissues such as skin, muscle, plasma membrane, and most types of cells. Although known isoforms of Plec is well-characterized in muscle dystrophy, very little is known on the function of Plec in the skeletal muscle development. Here, we found that Plec plays a vital role in promoting C2C12 myoblasts differentiation and proliferation, but inhibits their apoptosis. Also, Plec regulates the expression of atrophy-related genes (atrogin-1 and muRF-1) to rescue muscle atrophy. Furthermore, we have demonstrated that Plec binds to Dishevelled-2 (Dvl-2) and forms a protein complex, which is then activate the canonical Wnt signaling. We also observed that Plec resists ubiquitination by stabilizing Dvl-2 and reduces the level of LC3-labeled Dvl-2 and antagonizes the autophagy system. In conclusion, our findings suggest that Plec regulates canonical Wnt signaling mediated skeletal development by stabilizing Dvl-2 and downregulating the cellular autophagic degradation system.