期刊
JOURNAL OF CELL SCIENCE
卷 127, 期 24, 页码 5204-5217出版社
COMPANY BIOLOGISTS LTD
DOI: 10.1242/jcs.150961
关键词
Proteasome; Autophagy; Skeletal muscle; Muscle atrophy
类别
资金
- Japanese Ministry of Health, Labor and Welfare
- National Center of Neurology and Psychiatry
- Japanese Ministry of Education, Culture, Sports, Science and Technology [22659167, 24659421]
- Sasagawa Scientific Research Grant
- Takeda Science Foundation
- Nakatomi Foundation
- Grants-in-Aid for Scientific Research [24659421, 22659167, 26350979] Funding Source: KAKEN
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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