Development of Small GTPase with Photoswitching system and its application to photocontrol of intramolecular cell signaling

2018 Fiscal Year Final Research Report

• Project/Area Number: 15K07060
• Research Category: Grant-in-Aid for Scientific Research (C)
• Allocation Type: Multi-year Fund
• Section: 一般
• Research Field: Cell biology
• Research Institution: Soka University
• Principal Investigator: Maruta Shinsaku 創価大学, 理工学部, 教授 (40231732)
• Research Collaborator: UMEKI NOBUHISA
• Project Period (FY): 2015-04-01 – 2019-03-31
• Keywords: 低分子量Gタンパク質 / 細胞内情報伝達 / 光制御 / フォトクロミック分子 / アゾベンゼン / 制御因子 / ペプチド

Outline of Final Research Achievements

Ras is one of the small GTPase that regulates key cell functions such as cell proliferation and differentiation, gene expression, and cell adhesion. In addition, mutations at the amino acids involved in GTP hydrolysis has been shown to induce canceration of cells. Since the structure of Ras and its molecular mechanism as a biomolecular machine have been well studied, it will be possible to control of cell function if Ras can be regulated by an artificial external stimulus utilizing the ingenious mechanism of Ras. In this study, we attempted to control the function of Ras reversibly by introducing photo responsive photochromic molecules as a light switch into the mechanical mechanism of Ras and the regulating factor of Ras. And we clarified that the GTPase activity of Ras is controlled reversibly. In addition, it was shown that this photochromic peptide can be used to control the GDP-GTP exchange reaction of Ras in a photoreversible manner.

Free Research Field

生物物理

Academic Significance and Societal Importance of the Research Achievements

本研究では、重要な生理機能を担う低分子量G-蛋白質Rasを、情報伝達系の生体分子機械として捉え、その分子機械的仕組みに積極的に外部刺激応答性ナノデバイスを導入して人工的外部刺激で、Rasの細胞内情報伝達機能が制御出来る事を示した。このことにより、細胞の増殖、分化を人工的外部刺激で調節することが可能になると期待される。このRasの情報伝達機能を人工的に制御する方法を確立することにより、他の細胞機能を調節している低分子量G-蛋白質ファミリーへの応用も可能となる。細胞機能全体を人工的に制御するこの研究により、分子細胞の研究分野ばかりではなく医療分野へ貢献できることが強く期待できる。