Cargando…

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

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 prese...

Descripción completa

Detalles Bibliográficos
Autores principales: Tokutake, Yukako, Yamada, Keita, Ohata, Masaki, Obayashi, Yoshihito, Tsuchiya, Megumi, Yonekura, Shinichi
Formato: Online Artículo Texto
Lenguaje:English
Publicado: MDPI 2015
Materias:
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC4581263/
https://www.ncbi.nlm.nih.gov/pubmed/26266407
http://dx.doi.org/10.3390/ijms160818628
_version_ 1782391530803167232
author Tokutake, Yukako
Yamada, Keita
Ohata, Masaki
Obayashi, Yoshihito
Tsuchiya, Megumi
Yonekura, Shinichi
author_facet Tokutake, Yukako
Yamada, Keita
Ohata, Masaki
Obayashi, Yoshihito
Tsuchiya, Megumi
Yonekura, Shinichi
author_sort Tokutake, Yukako
collection PubMed
description 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.
format Online
Article
Text
id pubmed-4581263
institution National Center for Biotechnology Information
language English
publishDate 2015
publisher MDPI
record_format MEDLINE/PubMed
spelling pubmed-45812632015-09-28 ALS-Linked P56S-VAPB Mutation Impairs the Formation of Multinuclear Myotube in C2C12 Cells Tokutake, Yukako Yamada, Keita Ohata, Masaki Obayashi, Yoshihito Tsuchiya, Megumi Yonekura, Shinichi Int J Mol Sci Article 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. MDPI 2015-08-10 /pmc/articles/PMC4581263/ /pubmed/26266407 http://dx.doi.org/10.3390/ijms160818628 Text en © 2015 by the authors; licensee MDPI, Basel, Switzerland. This article is an open access article distributed under the terms and conditions of the Creative Commons Attribution license (http://creativecommons.org/licenses/by/4.0/).
spellingShingle Article
Tokutake, Yukako
Yamada, Keita
Ohata, Masaki
Obayashi, Yoshihito
Tsuchiya, Megumi
Yonekura, Shinichi
ALS-Linked P56S-VAPB Mutation Impairs the Formation of Multinuclear Myotube in C2C12 Cells
title ALS-Linked P56S-VAPB Mutation Impairs the Formation of Multinuclear Myotube in C2C12 Cells
title_full ALS-Linked P56S-VAPB Mutation Impairs the Formation of Multinuclear Myotube in C2C12 Cells
title_fullStr ALS-Linked P56S-VAPB Mutation Impairs the Formation of Multinuclear Myotube in C2C12 Cells
title_full_unstemmed ALS-Linked P56S-VAPB Mutation Impairs the Formation of Multinuclear Myotube in C2C12 Cells
title_short ALS-Linked P56S-VAPB Mutation Impairs the Formation of Multinuclear Myotube in C2C12 Cells
title_sort als-linked p56s-vapb mutation impairs the formation of multinuclear myotube in c2c12 cells
topic Article
url https://www.ncbi.nlm.nih.gov/pmc/articles/PMC4581263/
https://www.ncbi.nlm.nih.gov/pubmed/26266407
http://dx.doi.org/10.3390/ijms160818628
work_keys_str_mv AT tokutakeyukako alslinkedp56svapbmutationimpairstheformationofmultinuclearmyotubeinc2c12cells
AT yamadakeita alslinkedp56svapbmutationimpairstheformationofmultinuclearmyotubeinc2c12cells
AT ohatamasaki alslinkedp56svapbmutationimpairstheformationofmultinuclearmyotubeinc2c12cells
AT obayashiyoshihito alslinkedp56svapbmutationimpairstheformationofmultinuclearmyotubeinc2c12cells
AT tsuchiyamegumi alslinkedp56svapbmutationimpairstheformationofmultinuclearmyotubeinc2c12cells
AT yonekurashinichi alslinkedp56svapbmutationimpairstheformationofmultinuclearmyotubeinc2c12cells