| Project/Area Number |
18K19280
|
|---|
| Research Category |
Grant-in-Aid for Challenging Research (Exploratory)
|
| Allocation Type | Multi-year Fund |
|---|
| Review Section |
Medium-sized Section 43:Biology at molecular to cellular levels, and related fields
|
|---|
| Research Institution | Tohoku University |
|---|
Principal Investigator |
MIZUNO Kensaku 東北大学, 生命科学研究科, 名誉教授 (70128396)
|
|---|
| Project Period (FY) |
2018-06-29 – 2020-03-31
|
| Project Status |
Completed (Fiscal Year 2019)
|
| Budget Amount *help |
¥6,240,000 (Direct Cost: ¥4,800,000、Indirect Cost: ¥1,440,000)
Fiscal Year 2019: ¥3,120,000 (Direct Cost: ¥2,400,000、Indirect Cost: ¥720,000)
Fiscal Year 2018: ¥3,120,000 (Direct Cost: ¥2,400,000、Indirect Cost: ¥720,000)
|
|---|
| Keywords | 細胞骨格 / メカニカルストレス / アクチン / Rho / Rho-GEF |
|---|
| Outline of Final Research Achievements |
Mechanical force-induced cytoskeletal reorganization is essential for tissue remodeling and homeostasis. Solo is a RhoA-targeting Rho-GEF that is required for mechanical force-induced cytoskeletal reorganization. In this project, we aimed to elucidate activation mechanisms and cellular functions of Solo and obtained several findings as follows: 1) Solo is involved in hemidesmosome formation by binding to b4-integrin. 2) Solo and keratin-8/18 are required for the formation of the elongated morphology of epithelial tubules and the collective migration of epithelial cells. 3) The four leucine residues in the N-terminal Solo domain of Solo is required for its keratin-binding ability and the keratin-binding ability of Solo is critical for its cellular function in mechanotransduction. 4) Using BioID techniques, we identified Carmil-3 and Talin as the Solo-binding proteins.
|
| Academic Significance and Societal Importance of the Research Achievements |
細胞は、外界からの力学的刺激に応答して、形態、運動能、増殖・分化能を大きく変化させる。このような力学的刺激に対する細胞応答は、血管の恒常性、筋肉や骨の発達、幹細胞の運命決定、胚発生など、組織の形成や恒常性維持に重要な役割を果たしており、その応答不全は多くの疾患に関与している。本研究では、細胞の力覚応答に関与する分子であるSoloの活性化の分子機構に関する新しい知見を得た。また、管腔形成や集団移動におけるSoloの役割を解明した。これらの成果は、細胞の力覚応答の制御機構の解明と細胞の集団行動の分子機構の解明につながる成果であり、基礎生物学の進展だけでなく医学分野にも貢献すると考えられる。
|
