ALS-Linked P56S-VAPB Mutation Impairs the Formation of Multinuclear Myotube in C2C12 Cells
AbstractAmyotrophic lateral sclerosis (ALS) is a rapidly progressive neurodegenerative disorder that affects upper and lower motor neurons. Since motor neurons target skeletal muscles, the maintenance system of muscles is disturbed in ALS; however, the mechanism by which this occurs is unknown. In the present study, we investigated the effects of ALS-associated P56S-vesicle-associated membrane protein-associated protein B (VAPB) (P56S-VAPB) on the IRE1-XBP1 pathway, which is involved in the unfolded protein response (UPR) of the mouse myoblast cell line (C2C12 cells). Experiments with C2C12 cells transfected with wild-type wt-VAPB and P56S-VAPB expression vectors showed reduced myotube formation and aberrant myonuclear position in cells expressing P56S-VAPB. Activity of the IRE1-XBP1 pathway in the cells visualized with the ERAI system revealed that the pathway was disrupted in cells expressing P56S-VAPB, whereas the IRE1-XBP1 pathway activity was enhanced in the differentiation process of normal C2C12 cells. These results suggest that disruption of the IRE1-XBP1 pathway is a cause for the reduced myotube formation in P56S-VAPB-expressing cells. The expression level of the VAPB protein has been reported to be reduced in the neurons of patients with ALS. Therefore, it is expected that the IRE1-XBP1 pathway is also impaired in muscle tissues of patients with ALS, which causes a disturbance in the muscle maintenance system. View Full-Text
- Supplementary File 1:
Supplementary Information (PDF, 1634 KB)
Share & Cite This Article
Tokutake, Y.; Yamada, K.; Ohata, M.; Obayashi, Y.; Tsuchiya, M.; Yonekura, S. ALS-Linked P56S-VAPB Mutation Impairs the Formation of Multinuclear Myotube in C2C12 Cells. Int. J. Mol. Sci. 2015, 16, 18628-18641.
Tokutake Y, Yamada K, Ohata M, Obayashi Y, Tsuchiya M, Yonekura S. ALS-Linked P56S-VAPB Mutation Impairs the Formation of Multinuclear Myotube in C2C12 Cells. International Journal of Molecular Sciences. 2015; 16(8):18628-18641.Chicago/Turabian Style
Tokutake, Yukako; Yamada, Keita; Ohata, Masaki; Obayashi, Yoshihito; Tsuchiya, Megumi; Yonekura, Shinichi. 2015. "ALS-Linked P56S-VAPB Mutation Impairs the Formation of Multinuclear Myotube in C2C12 Cells." Int. J. Mol. Sci. 16, no. 8: 18628-18641.