Molecular mechanism of epithelial sheet formation and its repair through the tight junction

2023 Fiscal Year Final Research Report

• Project/Area Number: 21H02684
• Research Category: Grant-in-Aid for Scientific Research (B)
• Allocation Type: Single-year Grants
• Section: 一般
• Review Section: Basic Section 48040:Medical biochemistry-related
• Research Institution: The University of Tokushima
• Principal Investigator: YONEMURA Shigenobu 徳島大学, 大学院医歯薬学研究部(医学域), 教授 (60192811)
• Project Period (FY): 2021-04-01 – 2024-03-31
• Keywords: タイトジャンクション / 上皮シート / ミオシン / アクチン

Outline of Final Research Achievements

Because I have already noticed the intimate relationship between myosin activity and tight junction formation, I performed several gene knock down experiments which might be involved in the regulation of myosin activity. Galpha12/13 are known to regulate actin cytoskeleton through myosin activity and their knock down lead to TJ formation failure together with the incomplete formation of adherens junctions (AJ). Similarly, ROCK I was found to be important in maturing AJs resulting in TJ formation failure. Tension generated by actomyosin constriction appears to be involved in the wound closure movement of epithelial sheets. Live imaging of epithelial cells using laser ablation and magnetic beads showed that cells sense the degree of tension and respond to tension to facilitate wound closure movement.

Free Research Field

細胞生物学

Academic Significance and Societal Importance of the Research Achievements

AJ形成には初期段階と成熟段階があり、AJの成熟を経てTJができるのが通常の過程である。今回見出したGalpha12/13はAJの成熟がかなり遅れているように観察された。これまで、Galpha12/13がTJ形成に重要であるという報告はあったが、TJに直接影響しているのではなく、AJ成熟に重要であることが明らかになった。これまで、ミオシンの活性を制御しうる候補が提唱されてきたが、このようなAJ形成の特別な過程に重要というものはなく、細胞間接着装置形成、上皮シート形成の分子機構を理解する上で、今後の研究の展開に深く関わる知見が得られた。