Inducible Rpt3, a Proteasome Component, Knockout in Adult Skeletal Muscle Results in Muscle Atrophy

Yasuo Kitajima, Naoki Suzuki, Kiyoshi Yoshioka, Rumiko Izumi, Maki Tateyama, Yoshitaka Tashiro, Ryosuke Takahashi, Masashi Aoki, Yusuke Ono

Research output: Contribution to journalArticlepeer-review

1 Citation (Scopus)

Abstract

The ubiquitin–proteasome system has the capacity to degrade polyubiquitinated proteins and plays an important role in many cellular processes. However, the role of Rpt3, a crucial proteasomal gene, has not been investigated in adult muscles in vivo. Herein, we generated skeletal-muscle-specific Rpt3 knockout mice, in which genetic inactivation of Rpt3 could be induced by doxycycline administration. The Rpt3-knockout mice showed a significant reduction by more than 90% in the expression of Rpt3 in adult muscles. Using this model, we found that proteasome dysfunction in adult muscles resulted in muscle wasting and a decrease in the myofiber size. Immunoblotting analysis showed that the amounts of ubiquitinated proteins were markedly higher in muscles of Rpt3-deficient mice than in those of the control mice. Analysis of the autophagy pathway in the Rpt3-deficient mice showed that the upregulation of LC3II, p62, Atg5, Atg7, and Beclin-1 in protein levels, which supposed to be compensatory proteolysis activation. Our results suggest that the proteasome inhibition in adult muscle severely deteriorates myofiber integrity and results in muscle atrophy.

Original languageEnglish
Article number859
JournalFrontiers in Cell and Developmental Biology
Volume8
DOIs
Publication statusPublished - 2020 Sep 2

Keywords

  • Rpt3
  • adult skeletal muscle
  • muscle atrophy
  • muscle homeostasis
  • sarcopenia
  • ubiquitin proteasome system

ASJC Scopus subject areas

  • Developmental Biology
  • Cell Biology

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