Proteasome dysfunction induces muscle growth defects and protein aggregation
The ubiquitin-proteasome and autophagy-lysosome pathways are the two major routes of protein and organelle clearance. The role of the proteasome pathway in mammalian muscle has not been examined in vivo. In this study, we report that the muscle-specific deletion of a crucial proteasomal gene, Rpt3 (...
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Published in | Journal of cell science Vol. 127; no. Pt 24; pp. 5204 - 5217 |
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Main Authors | , , , , , , , , , , , , , , , |
Format | Journal Article |
Language | English |
Published |
England
The Company of Biologists
15.12.2014
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Subjects | |
Online Access | Get full text |
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Summary: | The ubiquitin-proteasome and autophagy-lysosome pathways are the two major routes of protein and organelle clearance. The role of the proteasome pathway in mammalian muscle has not been examined in vivo. In this study, we report that the muscle-specific deletion of a crucial proteasomal gene, Rpt3 (also known as Psmc4), resulted in profound muscle growth defects and a decrease in force production in mice. Specifically, developing muscles in conditional Rpt3-knockout animals showed dysregulated proteasomal activity. The autophagy pathway was upregulated, but the process of autophagosome formation was impaired. A microscopic analysis revealed the accumulation of basophilic inclusions and disorganization of the sarcomeres in young adult mice. Our results suggest that appropriate proteasomal activity is important for muscle growth and for maintaining myofiber integrity in collaboration with autophagy pathways. The deletion of a component of the proteasome complex contributed to myofiber degeneration and weakness in muscle disorders that are characterized by the accumulation of abnormal inclusions. |
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Bibliography: | ObjectType-Article-1 SourceType-Scholarly Journals-1 ObjectType-Feature-2 content type line 23 Present Address: Department of Stem Cell and Regenerative Biology, Harvard University, Cambridge MA 02138, USA. These authors contributed equally to this work Present Address: SK Project, Medical Innovation Center, Kyoto University. Kyoto University Graduate School of Medicine, Kyoto 606-8501, Japan. |
ISSN: | 0021-9533 1477-9137 |
DOI: | 10.1242/jcs.150961 |