Molecular mechanisms for proliferation-differentiation switch of skeletal muscle stem cells in response to metabolic signaling

• Project/Area Number: 15K18766
• Research Category: Grant-in-Aid for Young Scientists (B)
• Allocation Type: Multi-year Fund
• Research Field: Animal production science
• Research Institution: The University of Tokyo
• Principal Investigator: Yoneyama Yosuke 東京大学, 大学院農学生命科学研究科(農学部), 特任研究員 (10748289)
• Project Period (FY): 2015-04-01 – 2017-03-31
• Project Status: Completed (Fiscal Year 2016)
• Budget Amount: ¥4,290,000 (Direct Cost: ¥3,300,000、Indirect Cost: ¥990,000); Fiscal Year 2016: ¥2,080,000 (Direct Cost: ¥1,600,000、Indirect Cost: ¥480,000); Fiscal Year 2015: ¥2,210,000 (Direct Cost: ¥1,700,000、Indirect Cost: ¥510,000)
• Keywords: インスリン様成長因子 / インスリン受容体基質 / アセチル化

Outline of Final Research Achievements

Myogenic precursor cells contribute to the development of skeletal muscle as well as regeneration after injury. Insulin-like growth factor is an important hormone that regulates the function of myogenic precursor cells including proliferation and differentiation. In this study, we showed that insulin receptor substrate, a mediator of insulin-like growth factor signaling, is acetylated in response to metabolic activity of myogenic precursor cells. We identified a set of enzymes that acetylate or deacetylate insulin receptor substrate. Our study revealed a potential mechanism in which insulin-like growth factor signaling is modulated during myogenesis to coordinate the fate decision of myogenic precursor cells.

Research Products

• [Journal Article] Glucose deprivation attenuates sortilin levels in skeletal muscle cells (2017)
  • Author(s): Ariga M, Yoneyama Y, Fukushima T, Ishiuchi Y, Ishii T, Sato H, Hakuno F, Nedachi T, Takahashi S
  • Journal Title: Endocrine Journal Volume: 64 Issue: 3 Pages: 255-268
  • DOI: 10.1507/endocrj.EJ16-0319
  • NAID: 130005529466
  • ISSN: 0918-8959, 1348-4540
  • Peer Reviewed / Open Access
• [Journal Article] Analysis of insulin receptor substrates signaling dynamics on microstructured surfaces. (2015)
  • Author(s): Lanzerstorfer P, Yoneyama Y, Hakuno F, Muller U, Hoglinger O, Takahashi SI, Weghuber J
  • Journal Title: FEBS J. Volume: 282 Issue: 6 Pages: 987-1005
  • DOI: 10.1111/febs.13213
  • Peer Reviewed
• [Journal Article] The Novel Functions of High-Molecular-Mass Complexes Containing Insulin Receptor Substrates in Mediation and Modulation of Insulin-Like Activities: Emerging Concept of Diverse Functions by IRS-Associated Proteins. (2015)
  • Author(s): Hakuno F, Fukushima T, Yoneyama Y, Kamei H, Ozoe A, Yoshihara H, Yamanaka D, Shibano T, Sone-Yonezawa M, Yu BC, Chida K, Takahashi S.
  • Journal Title: Front Endocrinol (Lausanne). Volume: 6 Pages: 73-73
  • DOI: 10.3389/fendo.2015.00073
  • Peer Reviewed / Open Access / Int'l Joint Research / Acknowledgement Compliant
• [Presentation] Prolonged IGF signaling by IRS-1-mediated control of delayed IGF-IR internalization (2017)
  • Author(s): Yoneyama Y, Lanzerstorfer P, Weghuber J, Hakuno F, Takahashi S
  • Organizer: Gordon Research Conference: IGF & Insulin System in Physiology & Disease
  • Place of Presentation: Ventura, CA, USA
  • Year and Date: 2017-03-12
  • Int'l Joint Research
• [Presentation] Early embryonic insulin receptor substrate-1 signaling underpins neural crest cell survival contributing to catch-up growth induced by changing environmental oxygen tension in developing zebrafish (2017)
  • Author(s): Kamei H, Yoneyama Y, Hakuno F, Sawada R, Shimizu T, Duan C, Takahashi S
  • Organizer: Gordon Research Conference: IGF & Insulin System in Physiology & Disease
  • Place of Presentation: Ventura, CA, USA
  • Year and Date: 2017-03-12
  • Int'l Joint Research
• [Presentation] The SCF-b-TRCP E3 ligase complex induces IRS-1 degradation mediated by mTORC1 pathway (2017)
  • Author(s): Inamitsu T, Yoneyama Y, Chida K, Hakuno F, Takahashi S
  • Organizer: Gordon Research Conference: IGF & Insulin System in Physiology & Disease
  • Place of Presentation: Ventura, CA, USA
  • Year and Date: 2017-03-12
  • Int'l Joint Research
• [Presentation] Roles of IRS-1-induced cell competition in myogenic differentiation (2017)
  • Author(s): Usui A, Hakuno F, Yoneyama Y, Kamei H, Chida K, Takahashi S
  • Organizer: Gordon Research Conference: IGF & Insulin System in Physiology & Disease
  • Place of Presentation: Ventura, CA, USA
  • Year and Date: 2017-03-12
  • Int'l Joint Research
• [Presentation] Analysis of receptor tyrosine kinases and G-protein coupled receptor signaling dyanamics on micro-structured surfaces (2017)
  • Author(s): Lanzerstorfer P, Yoneyama Y, Hakuno F, Zindel D, Muller U, Krasel C, Buenemann M, Hoeglinger O, Takahashi S, Weghuber J
  • Organizer: Biophysical Society 61th Annual Meeting
  • Place of Presentation: New Orleans, LA, USA
  • Year and Date: 2017-02-11
  • Int'l Joint Research
• [Presentation] Temporal regulation of insulin-like growth factor signaling by IRS-1-dependent feedback loops (2017)
  • Author(s): Yoneyama Y
  • Organizer: Insulin-like signaling and nutrient signaling: universal signaling for extention of healthy lifespan and improvement of quality for humans and animals
  • Place of Presentation: The University of Tokyo, Tokyo, Japan
  • Year and Date: 2017-01-24
  • Int'l Joint Research / Invited
• [Presentation] SCFユビキチンリガーゼ複合体によるリン酸化依存的なインスリン受容体基質の分解制御 (2016)
  • Author(s): 稲光智美、米山鷹介、千田和広、伯野史彦、高橋伸一郎
  • Organizer: 第39回日本分子生物学会年会
  • Place of Presentation: パシフィコ横浜（神奈川県横浜市）
  • Year and Date: 2016-11-30
• [Remarks] 動物細胞制御制御学研究室
  • URL: http://endo.ar.a.u-tokyo.ac.jp/shingroup/index.html