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Proteomic Analysis Reveals New Cardiac-Specific Dystrophin-Associated Proteins
Mutations affecting the expression of dystrophin result in progressive loss of skeletal muscle function and cardiomyopathy leading to early mortality. Interestingly, clinical studies revealed no correlation in disease severity or age of onset between cardiac and skeletal muscles, suggesting that dys...
Autores principales: | , , , , , , , |
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Formato: | Online Artículo Texto |
Lenguaje: | English |
Publicado: |
Public Library of Science
2012
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Materias: | |
Acceso en línea: | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC3427372/ https://www.ncbi.nlm.nih.gov/pubmed/22937058 http://dx.doi.org/10.1371/journal.pone.0043515 |
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author | Johnson, Eric K. Zhang, Liwen Adams, Marvin E. Phillips, Alistair Freitas, Michael A. Froehner, Stanley C. Green-Church, Kari B. Montanaro, Federica |
author_facet | Johnson, Eric K. Zhang, Liwen Adams, Marvin E. Phillips, Alistair Freitas, Michael A. Froehner, Stanley C. Green-Church, Kari B. Montanaro, Federica |
author_sort | Johnson, Eric K. |
collection | PubMed |
description | Mutations affecting the expression of dystrophin result in progressive loss of skeletal muscle function and cardiomyopathy leading to early mortality. Interestingly, clinical studies revealed no correlation in disease severity or age of onset between cardiac and skeletal muscles, suggesting that dystrophin may play overlapping yet different roles in these two striated muscles. Since dystrophin serves as a structural and signaling scaffold, functional differences likely arise from tissue-specific protein interactions. To test this, we optimized a proteomics-based approach to purify, identify and compare the interactome of dystrophin between cardiac and skeletal muscles from as little as 50 mg of starting material. We found selective tissue-specific differences in the protein associations of cardiac and skeletal muscle full length dystrophin to syntrophins and dystrobrevins that couple dystrophin to signaling pathways. Importantly, we identified novel cardiac-specific interactions of dystrophin with proteins known to regulate cardiac contraction and to be involved in cardiac disease. Our approach overcomes a major challenge in the muscular dystrophy field of rapidly and consistently identifying bona fide dystrophin-interacting proteins in tissues. In addition, our findings support the existence of cardiac-specific functions of dystrophin and may guide studies into early triggers of cardiac disease in Duchenne and Becker muscular dystrophies. |
format | Online Article Text |
id | pubmed-3427372 |
institution | National Center for Biotechnology Information |
language | English |
publishDate | 2012 |
publisher | Public Library of Science |
record_format | MEDLINE/PubMed |
spelling | pubmed-34273722012-08-30 Proteomic Analysis Reveals New Cardiac-Specific Dystrophin-Associated Proteins Johnson, Eric K. Zhang, Liwen Adams, Marvin E. Phillips, Alistair Freitas, Michael A. Froehner, Stanley C. Green-Church, Kari B. Montanaro, Federica PLoS One Research Article Mutations affecting the expression of dystrophin result in progressive loss of skeletal muscle function and cardiomyopathy leading to early mortality. Interestingly, clinical studies revealed no correlation in disease severity or age of onset between cardiac and skeletal muscles, suggesting that dystrophin may play overlapping yet different roles in these two striated muscles. Since dystrophin serves as a structural and signaling scaffold, functional differences likely arise from tissue-specific protein interactions. To test this, we optimized a proteomics-based approach to purify, identify and compare the interactome of dystrophin between cardiac and skeletal muscles from as little as 50 mg of starting material. We found selective tissue-specific differences in the protein associations of cardiac and skeletal muscle full length dystrophin to syntrophins and dystrobrevins that couple dystrophin to signaling pathways. Importantly, we identified novel cardiac-specific interactions of dystrophin with proteins known to regulate cardiac contraction and to be involved in cardiac disease. Our approach overcomes a major challenge in the muscular dystrophy field of rapidly and consistently identifying bona fide dystrophin-interacting proteins in tissues. In addition, our findings support the existence of cardiac-specific functions of dystrophin and may guide studies into early triggers of cardiac disease in Duchenne and Becker muscular dystrophies. Public Library of Science 2012-08-24 /pmc/articles/PMC3427372/ /pubmed/22937058 http://dx.doi.org/10.1371/journal.pone.0043515 Text en © 2012 Johnson 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 Johnson, Eric K. Zhang, Liwen Adams, Marvin E. Phillips, Alistair Freitas, Michael A. Froehner, Stanley C. Green-Church, Kari B. Montanaro, Federica Proteomic Analysis Reveals New Cardiac-Specific Dystrophin-Associated Proteins |
title | Proteomic Analysis Reveals New Cardiac-Specific Dystrophin-Associated Proteins |
title_full | Proteomic Analysis Reveals New Cardiac-Specific Dystrophin-Associated Proteins |
title_fullStr | Proteomic Analysis Reveals New Cardiac-Specific Dystrophin-Associated Proteins |
title_full_unstemmed | Proteomic Analysis Reveals New Cardiac-Specific Dystrophin-Associated Proteins |
title_short | Proteomic Analysis Reveals New Cardiac-Specific Dystrophin-Associated Proteins |
title_sort | proteomic analysis reveals new cardiac-specific dystrophin-associated proteins |
topic | Research Article |
url | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC3427372/ https://www.ncbi.nlm.nih.gov/pubmed/22937058 http://dx.doi.org/10.1371/journal.pone.0043515 |
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