Elucidation of gradient sensing mechanism in chemotactic signaling system

2023 Fiscal Year Final Research Report

• Project/Area Number: 19H00982
• Research Category: Grant-in-Aid for Scientific Research (A)
• Allocation Type: Single-year Grants
• Section: 一般
• Review Section: Medium-sized Section 43:Biology at molecular to cellular levels, and related fields
• Research Institution: Osaka University
• Principal Investigator: Ueda Masahiro 大阪大学, 大学院生命機能研究科, 教授 (40444517)
• Project Period (FY): 2019-04-01 – 2024-03-31
• Keywords: 走化性 / GPCR / 三量体Gタンパク質 / アレスチン / 適応 / 細胞性粘菌 / 極性形成 / １分子イメージング

Outline of Final Research Achievements

Eukaryotic chemotaxis plays an important role as a cellular function to control the direction of cell motility in environmental exploration of unicellular organisms and in development and immune responses of multicellular organisms. In this study, we analyzed the intracellular spatiotemporal dynamics of signaling molecules involved in chemotaxis using super-resolution and single-molecule microscopy to elucidate the gradient sensing mechanism. We revealed the mechanism by which the concentration gradient is recognized over a wide concentration range, which includes not only phosphorylation of GPCR-type chemoattractant receptors, but also regulation of the activity as well as the membrane-cytosol shuttling of G proteins and lateral diffusion on the membrane of G proteins. In addition, novel findings were obtained on the excitable system that acts to amplify the gradient signals, and we proposed a new mechanism of 1/0 signal formation, which we termed "dynamic partitioning".

Free Research Field

生物物理学

Academic Significance and Societal Importance of the Research Achievements

本研究を通して明らかとなった広い濃度域にわたる濃度勾配認識の仕組みやダイナミックパーティショニングの仕組みは、下等真核生物である細胞性粘菌において初めて発見された仕組みであり、現在のところ普遍性は明らかになっていない。しかしながら、走化性シグナル伝達系はヒト免疫細胞を含む様々な真核生物で広く保存されていることから、他の細胞種においても同様の制御機構が働く可能性が示唆される。またGPCRは細胞内シグナル伝達において中心的な役割を果たしていることから、新たな制御メカニズムの基礎的な発見と解明は、医科学・創薬などにおける疾患の原因究明や治療薬の開発を進める上で不可欠な意義を有する。