| First Author | Kitajima Y | Year | 2014 |
| Journal | J Cell Sci | Volume | 127 |
| Issue | Pt 24 | Pages | 5204-17 |
| PubMed ID | 25380823 | Mgi Jnum | J:218217 |
| Mgi Id | MGI:5616993 | Doi | 10.1242/jcs.150961 |
| Citation | Kitajima Y, et al. (2014) Proteasome dysfunction induces muscle growth defects and protein aggregation. J Cell Sci 127(24):5204-17 |
| abstractText | 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. |
