Next Article in Journal
Bioactive Compounds of Blueberries: Post-Harvest Factors Influencing the Nutritional Value of Products
Next Article in Special Issue
Genetic Polymorphisms of Glutathione-Related Enzymes (GSTM1, GSTT1, and GSTP1) and Schizophrenia Risk: A Meta-Analysis
Previous Article in Journal
Role of Pharmacogenetics in Hematopoietic Stem Cell Transplantation Outcome in Children
Previous Article in Special Issue
Impaired Focal Adhesion Kinase-Grb2 Interaction during Elevated Activity in Hippocampal Neurons
Article Menu
Issue 8 (August) cover image

Export Article

Open AccessArticle
Int. J. Mol. Sci. 2015, 16(8), 18628-18641; doi:10.3390/ijms160818628

ALS-Linked P56S-VAPB Mutation Impairs the Formation of Multinuclear Myotube in C2C12 Cells

1
Interdisciplinary Graduate School of Science and Technology, Shinshu University, 8304 Minamiminowa, Kamiina, Nagano 399-4598, Japan
2
Graduate School of Agriculture, Shinshu University, 8304 Minamiminowa, Kamiina, Nagano 399-4598, Japan
3
Department of Interdisciplinary Genome Sciences and Cell Metabolism, Institute for Biomedical Sciences, Interdisciplinary Cluster for Cutting Edge Research (ICCER), Shinshu University, 8304 Minamiminowa, Kamiina, Nagano 399-4598, Japan
*
Author to whom correspondence should be addressed.
Academic Editor: Kurt A. Jellinger
Received: 19 June 2015 / Revised: 24 July 2015 / Accepted: 30 July 2015 / Published: 10 August 2015
(This article belongs to the Special Issue Mechanisms of Neurodegeneration)
View Full-Text   |   Download PDF [2630 KB, uploaded 10 August 2015]   |  

Abstract

Amyotrophic 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
Keywords: amyotrophic lateral sclerosis; satellite cells; vesicle-associated membrane protein associated protein B; differentiation; unfolded protein response amyotrophic lateral sclerosis; satellite cells; vesicle-associated membrane protein associated protein B; differentiation; unfolded protein response
Figures

This is an open access article distributed under the Creative Commons Attribution License which permits unrestricted use, distribution, and reproduction in any medium, provided the original work is properly cited. (CC BY 4.0).

Supplementary material

Scifeed alert for new publications

Never miss any articles matching your research from any publisher
  • Get alerts for new papers matching your research
  • Find out the new papers from selected authors
  • Updated daily for 49'000+ journals and 6000+ publishers
  • Define your Scifeed now

SciFeed Share & Cite This Article

MDPI and ACS Style

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.

Show more citation formats Show less citations formats

Related Articles

Article Metrics

Article Access Statistics

1

Comments

[Return to top]
Int. J. Mol. Sci. EISSN 1422-0067 Published by MDPI AG, Basel, Switzerland RSS E-Mail Table of Contents Alert
Back to Top