Analysis for conformational change of JRAB regulating collective cell migration; from molecular information to physiological role in mouse

2019 Fiscal Year Final Research Report

• Project/Area Number: 17K08636
• Research Category: Grant-in-Aid for Scientific Research (C)
• Allocation Type: Multi-year Fund
• Section: 一般
• Research Field: General medical chemistry
• Research Institution: The University of Tokushima
• Principal Investigator: SAKANE Ayuko 徳島大学, 大学院医歯薬学研究部(医学域), 准教授 (60509777)
• Project Period (FY): 2017-04-01 – 2020-03-31
• Keywords: JRAB / 1分子構造変化 / 蛋白質間相互作用 / 集団的細胞運動 / 階層的解析

Outline of Final Research Achievements

JRAB/MICAL-L2 engages in intramolecular interaction between the N-terminal LIM domain and the C-terminal coiled-coil domain. The conformational change of JRAB/MICAL-L2 participates in multiple rearrangements of the actin cytoskeleton involved in various biological processes. In this work, we found that both the first and second zinc finger domains within the LIM domain bind to the first and second actin monomers, respectively, at minus end of the F-actin, resulting in the inhibition of F-actin depolymerization. The most important finding was that some amino acid residues of first zinc finger domain are involved in both its association with F-actin and the intramolecular interaction. Taken together, the actin cytoskeletal rearrangement via JRAB-LIM, such as the enhancement of ruffling, are fine-tuned by the intramolecular interaction between the first zinc finger domain and C-terminal domain.

Free Research Field

生化学、細胞生物学、分子生物学

Academic Significance and Societal Importance of the Research Achievements

集団的細胞運動は、胎生期の組織・器官形成や創傷治癒の過程だけでなく、がん転移の際にも広く認められる現象である。したがって、その制御機構を理解することは、生物学的および生理学的に重要であるだけでなく、発生異常の病態解明およびがん転移機構の解明につながる可能性が高く、医学への貢献が多いに期待される。また、本研究で得られた個体レベルでの成果を基に1分子の構造変化を標的にしたがん転移の抑制や再生医療への応用に向けた新たな技術開発の創出が実現する可能性があり、その社会的意義は大きい。