Author:
Kitajima Yasuo,Tashiro Yoshitaka,Suzuki Naoki,Warita Hitoshi,Kato Masaaki,Tateyama Maki,Ando Risa,Izumi Rumiko,Yamazaki Maya,Abe Manabu,Sakimura Kenji,Ito Hidefumi,Urushitani Makoto,Nagatomi Ryoichi,Takahashi Ryosuke,Aoki Masashi
Abstract
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, 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.
Publisher
The Company of Biologists
Cited by
62 articles.
订阅此论文施引文献
订阅此论文施引文献,注册后可以免费订阅5篇论文的施引文献,订阅后可以查看论文全部施引文献