Myofiber androgen receptor increases muscle strength mediated by a skeletal muscle splicing variant of Mylk4

Iori Sakakibara, Yuta Yanagihara, Koichi Himori, Takashi Yamada, Hiroshi Sakai, Yuichiro Sawada, Hirotaka Takahashi, Noritaka Saeki, Hiroyuki Hirakawa, Atsushi Yokoyama, So ichiro Fukada, Tatsuya Sawasaki, Yuuki Imai

Research output: Contribution to journalArticlepeer-review

1 Citation (Scopus)

Abstract

Androgens have a robust effect on skeletal muscles to increase muscle mass and strength. The molecular mechanism of androgen/androgen receptor (AR) action on muscle strength is still not well known, especially for the regulation of sarcomeric genes. In this study, we generated androgen-induced hypertrophic model mice, myofiber-specific androgen receptor knockout (cARKO) mice supplemented with dihydrotestosterone (DHT). DHT treatment increased grip strength in control mice but not in cARKO mice. Transcriptome analysis by RNA-seq, using skeletal muscles obtained from control and cARKO mice treated with or without DHT, identified a fast-type muscle-specific novel splicing variant of Myosin light-chain kinase 4 (Mylk4) as a target of AR in skeletal muscles. Mylk4 knockout mice exhibited decreased maximum isometric torque of plantar flexion and passive stiffness of myofibers due to reduced phosphorylation of Myomesin 1 protein. This study suggests that androgen-induced skeletal muscle strength is mediated with Mylk4 and Myomesin 1 axis.

Original languageEnglish
Article number102303
JournaliScience
Volume24
Issue number4
DOIs
Publication statusPublished - 2021 Apr 23

Keywords

  • Animal Physiology
  • Endocrinology
  • Molecular Biology
  • Molecular Physiology

ASJC Scopus subject areas

  • General

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