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Destabilization of the Dystrophin-Glycoprotein Complex without Functional Deficits in α-Dystrobrevin Null Muscle

α-Dystrobrevin is a component of the dystrophin-glycoprotein complex (DGC) and is thought to have both structural and signaling roles in skeletal muscle. Mice deficient for α-dystrobrevin (adbn(−/−)) exhibit extensive myofiber degeneration and neuromuscular junction abnormalities. However, the bioch...

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Autores principales: Bunnell, Tina M., Jaeger, Michele A., Fitzsimons, Daniel P., Prins, Kurt W., Ervasti, James M.
Formato: Texto
Lenguaje:English
Publicado: Public Library of Science 2008
Materias:
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC2432020/
https://www.ncbi.nlm.nih.gov/pubmed/18596960
http://dx.doi.org/10.1371/journal.pone.0002604
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author Bunnell, Tina M.
Jaeger, Michele A.
Fitzsimons, Daniel P.
Prins, Kurt W.
Ervasti, James M.
author_facet Bunnell, Tina M.
Jaeger, Michele A.
Fitzsimons, Daniel P.
Prins, Kurt W.
Ervasti, James M.
author_sort Bunnell, Tina M.
collection PubMed
description α-Dystrobrevin is a component of the dystrophin-glycoprotein complex (DGC) and is thought to have both structural and signaling roles in skeletal muscle. Mice deficient for α-dystrobrevin (adbn(−/−)) exhibit extensive myofiber degeneration and neuromuscular junction abnormalities. However, the biochemical stability of the DGC and the functional performance of adbn(−/−) muscle have not been characterized. Here we show that the biochemical association between dystrophin and β-dystroglycan is compromised in adbn(−/−) skeletal muscle, suggesting that α-dystrobrevin plays a structural role in stabilizing the DGC. However, despite muscle cell death and DGC destabilization, costamere organization and physiological performance is normal in adbn(−/−) skeletal muscle. Our results demonstrate that myofiber degeneration alone does not cause functional deficits and suggests that more complex pathological factors contribute to the development of muscle weakness in muscular dystrophy.
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spelling pubmed-24320202008-07-02 Destabilization of the Dystrophin-Glycoprotein Complex without Functional Deficits in α-Dystrobrevin Null Muscle Bunnell, Tina M. Jaeger, Michele A. Fitzsimons, Daniel P. Prins, Kurt W. Ervasti, James M. PLoS One Research Article α-Dystrobrevin is a component of the dystrophin-glycoprotein complex (DGC) and is thought to have both structural and signaling roles in skeletal muscle. Mice deficient for α-dystrobrevin (adbn(−/−)) exhibit extensive myofiber degeneration and neuromuscular junction abnormalities. However, the biochemical stability of the DGC and the functional performance of adbn(−/−) muscle have not been characterized. Here we show that the biochemical association between dystrophin and β-dystroglycan is compromised in adbn(−/−) skeletal muscle, suggesting that α-dystrobrevin plays a structural role in stabilizing the DGC. However, despite muscle cell death and DGC destabilization, costamere organization and physiological performance is normal in adbn(−/−) skeletal muscle. Our results demonstrate that myofiber degeneration alone does not cause functional deficits and suggests that more complex pathological factors contribute to the development of muscle weakness in muscular dystrophy. Public Library of Science 2008-07-02 /pmc/articles/PMC2432020/ /pubmed/18596960 http://dx.doi.org/10.1371/journal.pone.0002604 Text en Bunnell 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
Bunnell, Tina M.
Jaeger, Michele A.
Fitzsimons, Daniel P.
Prins, Kurt W.
Ervasti, James M.
Destabilization of the Dystrophin-Glycoprotein Complex without Functional Deficits in α-Dystrobrevin Null Muscle
title Destabilization of the Dystrophin-Glycoprotein Complex without Functional Deficits in α-Dystrobrevin Null Muscle
title_full Destabilization of the Dystrophin-Glycoprotein Complex without Functional Deficits in α-Dystrobrevin Null Muscle
title_fullStr Destabilization of the Dystrophin-Glycoprotein Complex without Functional Deficits in α-Dystrobrevin Null Muscle
title_full_unstemmed Destabilization of the Dystrophin-Glycoprotein Complex without Functional Deficits in α-Dystrobrevin Null Muscle
title_short Destabilization of the Dystrophin-Glycoprotein Complex without Functional Deficits in α-Dystrobrevin Null Muscle
title_sort destabilization of the dystrophin-glycoprotein complex without functional deficits in α-dystrobrevin null muscle
topic Research Article
url https://www.ncbi.nlm.nih.gov/pmc/articles/PMC2432020/
https://www.ncbi.nlm.nih.gov/pubmed/18596960
http://dx.doi.org/10.1371/journal.pone.0002604
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