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α-Syntrophin Modulates Myogenin Expression in Differentiating Myoblasts
BACKGROUND: α-Syntrophin is a scaffolding protein linking signaling proteins to the sarcolemmal dystrophin complex in mature muscle. However, α-syntrophin is also expressed in differentiating myoblasts during the early stages of muscle differentiation. In this study, we examined the relationship bet...
Autores principales: | , , , , , |
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Formato: | Texto |
Lenguaje: | English |
Publicado: |
Public Library of Science
2010
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Materias: | |
Acceso en línea: | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC3003685/ https://www.ncbi.nlm.nih.gov/pubmed/21179410 http://dx.doi.org/10.1371/journal.pone.0015355 |
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author | Kim, Min Jeong Hwang, Sung Ho Lim, Jeong A. Froehner, Stanley C. Adams, Marvin E. Kim, Hye Sun |
author_facet | Kim, Min Jeong Hwang, Sung Ho Lim, Jeong A. Froehner, Stanley C. Adams, Marvin E. Kim, Hye Sun |
author_sort | Kim, Min Jeong |
collection | PubMed |
description | BACKGROUND: α-Syntrophin is a scaffolding protein linking signaling proteins to the sarcolemmal dystrophin complex in mature muscle. However, α-syntrophin is also expressed in differentiating myoblasts during the early stages of muscle differentiation. In this study, we examined the relationship between the expression of α-syntrophin and myogenin, a key muscle regulatory factor. METHODS AND FINDINGS: The absence of α-syntrophin leads to reduced and delayed myogenin expression. This conclusion is based on experiments using muscle cells isolated from α-syntrophin null mice, muscle regeneration studies in α-syntrophin null mice, experiments in Sol8 cells (a cell line that expresses only low levels of α-syntrophin) and siRNA studies in differentiating C2 cells. In primary cultured myocytes isolated from α-syntrophin null mice, the level of myogenin was less than 50% that from wild type myocytes (p<0.005) 40 h after differentiation induction. In regenerating muscle, the expression of myogenin in the α-syntrophin null muscle was reduced to approximately 25% that of wild type muscle (p<0.005). Conversely, myogenin expression is enhanced in primary cultures of myoblasts isolated from a transgenic mouse over-expressing α-syntrophin and in Sol8 cells transfected with a vector to over-express α-syntrophin. Moreover, we find that myogenin mRNA is reduced in the absence of α-syntrophin and increased by α-syntrophin over-expression. Immunofluorescence microscopy shows that α-syntrophin is localized to the nuclei of differentiating myoblasts. Finally, immunoprecipitation experiments demonstrate that α-syntrophin associates with Mixed-Lineage Leukemia 5, a regulator of myogenin expression. CONCLUSIONS: We conclude that α-syntrophin plays an important role in regulating myogenesis by modulating myogenin expression. |
format | Text |
id | pubmed-3003685 |
institution | National Center for Biotechnology Information |
language | English |
publishDate | 2010 |
publisher | Public Library of Science |
record_format | MEDLINE/PubMed |
spelling | pubmed-30036852010-12-22 α-Syntrophin Modulates Myogenin Expression in Differentiating Myoblasts Kim, Min Jeong Hwang, Sung Ho Lim, Jeong A. Froehner, Stanley C. Adams, Marvin E. Kim, Hye Sun PLoS One Research Article BACKGROUND: α-Syntrophin is a scaffolding protein linking signaling proteins to the sarcolemmal dystrophin complex in mature muscle. However, α-syntrophin is also expressed in differentiating myoblasts during the early stages of muscle differentiation. In this study, we examined the relationship between the expression of α-syntrophin and myogenin, a key muscle regulatory factor. METHODS AND FINDINGS: The absence of α-syntrophin leads to reduced and delayed myogenin expression. This conclusion is based on experiments using muscle cells isolated from α-syntrophin null mice, muscle regeneration studies in α-syntrophin null mice, experiments in Sol8 cells (a cell line that expresses only low levels of α-syntrophin) and siRNA studies in differentiating C2 cells. In primary cultured myocytes isolated from α-syntrophin null mice, the level of myogenin was less than 50% that from wild type myocytes (p<0.005) 40 h after differentiation induction. In regenerating muscle, the expression of myogenin in the α-syntrophin null muscle was reduced to approximately 25% that of wild type muscle (p<0.005). Conversely, myogenin expression is enhanced in primary cultures of myoblasts isolated from a transgenic mouse over-expressing α-syntrophin and in Sol8 cells transfected with a vector to over-express α-syntrophin. Moreover, we find that myogenin mRNA is reduced in the absence of α-syntrophin and increased by α-syntrophin over-expression. Immunofluorescence microscopy shows that α-syntrophin is localized to the nuclei of differentiating myoblasts. Finally, immunoprecipitation experiments demonstrate that α-syntrophin associates with Mixed-Lineage Leukemia 5, a regulator of myogenin expression. CONCLUSIONS: We conclude that α-syntrophin plays an important role in regulating myogenesis by modulating myogenin expression. Public Library of Science 2010-12-17 /pmc/articles/PMC3003685/ /pubmed/21179410 http://dx.doi.org/10.1371/journal.pone.0015355 Text en Kim et al. http://creativecommons.org/licenses/by/4.0/ This is an open-access article distributed under the terms of the Creative Commons Attribution License, which permits unrestricted use, distribution, and reproduction in any medium, provided the original author and source are properly credited. |
spellingShingle | Research Article Kim, Min Jeong Hwang, Sung Ho Lim, Jeong A. Froehner, Stanley C. Adams, Marvin E. Kim, Hye Sun α-Syntrophin Modulates Myogenin Expression in Differentiating Myoblasts |
title | α-Syntrophin Modulates Myogenin Expression in Differentiating Myoblasts |
title_full | α-Syntrophin Modulates Myogenin Expression in Differentiating Myoblasts |
title_fullStr | α-Syntrophin Modulates Myogenin Expression in Differentiating Myoblasts |
title_full_unstemmed | α-Syntrophin Modulates Myogenin Expression in Differentiating Myoblasts |
title_short | α-Syntrophin Modulates Myogenin Expression in Differentiating Myoblasts |
title_sort | α-syntrophin modulates myogenin expression in differentiating myoblasts |
topic | Research Article |
url | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC3003685/ https://www.ncbi.nlm.nih.gov/pubmed/21179410 http://dx.doi.org/10.1371/journal.pone.0015355 |
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