Puromycin-sensitive aminopeptidase is required for C2C12 myoblast proliferation and differentiation

Shion Osana, Yasuo Kitajima, Naoki Suzuki, Aki Nunomiya, Hiroaki Takada, Takahiro Kubota, Kazutaka Murayama, Ryoichi Nagatomi

Research output: Contribution to journalArticlepeer-review

Abstract

The ubiquitin-proteasome system is a major protein degradation pathway in the cell. Proteasomes produce several peptides that are rapidly degraded to free amino acids by intracellular aminopeptidases. Our previous studies reported that proteolysis via proteasomes and aminopeptidases is required for myoblast proliferation and differentiation. However, the role of intracellular aminopeptidases in myoblast proliferation and differentiation had not been clarified. In this study, we investigated the effects of puromycin-sensitive aminopeptidase (PSA) on C2C12 myoblast proliferation and differentiation by knocking down PSA. Aminopeptidase enzymatic activity was reduced in PSA-knockdown myoblasts. Knockdown of PSA induced impaired cell cycle progression in C2C12 myoblasts and accumulation of cells at the G2/M phase. Additionally, after the induction of myogenic differentiation in PSA-knockdown myoblasts, multinucleated circular-shaped myotubes with impaired cell polarity were frequently identified. Cell division cycle 42 (CDC42) knockdown in myoblasts resulted in a loss of cell polarity and the formation of multinucleated circular-shaped myotubes, which were similar to PSA-knockdown myoblasts. These data suggest that PSA is required for the proliferation of myoblasts in the growth phase and for the determination of cell polarity and elongation of myotubes in the differentiation phase.

Original languageEnglish
Pages (from-to)5293-5305
Number of pages13
JournalJournal of Cellular Physiology
Volume236
Issue number7
DOIs
Publication statusPublished - 2021 Jul

Keywords

  • cell polarity
  • myoblast fusion
  • myogenic differentiation
  • proteasome
  • puromycin-sensitive aminopeptidase

ASJC Scopus subject areas

  • Physiology
  • Clinical Biochemistry
  • Cell Biology

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