Study of Rho family small G proteins in the increase of muscle size

2013 Fiscal Year Final Research Report

• Project/Area Number: 23700832
• Research Category: Grant-in-Aid for Young Scientists (B)
• Allocation Type: Multi-year Fund
• Research Field: Applied health science
• Research Institution: Kobe University
• Principal Investigator: UEDA Shuji 神戸大学, (連合)農学研究科(研究院), 助教 (50379400)
• Project Period (FY): 2011 – 2012
• Keywords: 加齢 / 老化 / RhoA / IGF-I / 筋肉 / DGK / heat shock protein / BirA

Outline of Final Research Achievements

Rho family GTPase RhoA has been known to be involved in the muscular development and reconstruction. However, the role of RhoA in IGF-1-induced muscular hypertrophy remain to be revealed. To investigate the regulatory mechanism of RhoA activation, we used muscular hypertrophy model of C2C12 cells. After IGF-I treatment, protein level of RhoA was upregulated, and activated RhoA was continuously increased in hypertrophic myotubes.RhoA dominant-negative mutant impaired prominent hypertrophy, and inhibited IGF-1-depending p38 MAPK activation and M-cadherin-shift, which are required for muscular differentiation.These results indicate that RhoA involves in multiple steps of IGF-I-induced muscular hypertrophy. To identify the key molecule in this mechanism, we designed RhoA tagged with promiscuous biotin ligase BirA and isolated several interesting RhoA binding candidate.
This study clarified one end of the activation mechanism of RhoA related to muscular hypertrophy by IGF-1.

Free Research Field

総合領域