Abstract
ABSTRACTMyoblast fusion is a highly regulated process that is essential for skeletal muscle formation during muscle development and regeneration in mammals. Much remains to be elucidated about the molecular mechanism of myoblast fusion although cadherins, which are Ca2+-dependent cell–cell adhesion molecules, are thought to play a critical role in this process. Mouse myoblasts lacking either N-cadherin or M-cadherin can still fuse to form myotubes, indicating that they have no specific function in this process and may be functionally replaced by either M-cadherin or N-cadherin, respectively. In this study, we show that expressing the E-cadherin cytoplasmic domain ectopically in C2C12 myoblasts inhibits cell surface localization of endogenous M-cadherin and N-cadherin, as well as cell–cell fusion. This domain, however, does not inhibit myoblast differentiation according to microarray-based gene expression analysis. In contrast, expressing a dominant-negative β-catenin mutant ectopically, which suppresses Wnt/β-catenin signaling, did not inhibit cell–cell fusion. Therefore, the E-cadherin cytoplasmic domain inhibits cell–cell fusion by inhibiting cell surface localization of endogenous cadherins and not by inhibiting Wnt/β-catenin signaling.
Highlights
The process by which muscle cells interact and fuse to produce syncytia has been studied for decades and yet remains poorly understood
The DECT-coding sequence was expressed under the control of the synthetic CAG promoter in mouse C2C12 myoblasts (Fig. 1B)
These results were consistent with our previous finding that DECT expression in epithelial MDCK cells blocks the transport of endogenous E-cadherin but not of gp135, an unrelated cell surface protein (Ozawa and Kobayashi, 2014)
Summary
The process by which muscle cells interact and fuse to produce syncytia has been studied for decades and yet remains poorly understood. Myoblasts of different species recognize one another, adhere and fuse to form heterokaryon myotubes, yet very rarely spontaneously fuse with cells from other tissues (Blau et al, 1983). Cadherins comprise a large family of Ca2+-dependent cell–cell adhesion molecules. E-cadherin, a prototypical member of this family, is a transmembrane protein that forms adherens junctions between epithelial cells. The cytoplasmic domain of cadherins interacts directly with either β-catenin or plakoglobin. These two molecules interact with α-catenin, and α-catenin links the cadherin–
Sign-in/Register to view highlights & summary Sign-in/Register to access full text options 
Talk to us
Join us for a 30 min session where you can share your feedback and ask us any queries you have
Schedule a callDisclaimer: All third-party content on this website/platform is and will remain the property of their respective owners and is provided on "as is" basis without any warranties, express or implied. Use of third-party content does not indicate any affiliation, sponsorship with or endorsement by them. Any references to third-party content is to identify the corresponding services and shall be considered fair use under The CopyrightLaw.
