Sensing of neighboring cell's death at tight junctions

2020 Fiscal Year Final Research Report

• Project/Area Number: 18H02617
• 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): 2018-04-01 – 2021-03-31
• Keywords: タイトジャンクション / 損傷修復 / ミオシン

Outline of Final Research Achievements

In this study, we aimed to test our hypothesis that sensing of the death of adjacent cells in polarized epithelial cell sheets involves tight junction formation and to examine the molecular mechanism. When adjacent cells are dead, actomyosin accumulates near the plasma membrane facing the dead cells and helps both wound closure and extrusion of dead cells. First, we found that this actomyosin accumulation is enhanced when tight junctions are not formed. We further tried understanding the molecular mechanism. At the wound closure of epithelial sheets, Rock2, a kinase for myosin regulatory light chain was found to be recruited to the dead/live cell border. Also, Shroom3 that recruits Rock2 became localized to the border. This would facilitate myosin activation at the border and accumulation of activated myosin filaments and interacting actin filaments.

Free Research Field

細胞生物学

Academic Significance and Societal Importance of the Research Achievements

本研究成果はアクトミオシンの収縮による損傷修復がタイトジャンクションを持つ上皮細胞に限られることをよく説明するばかりでなく、修復が完了すると不要となったアクトミオシンの集積が自動的に解消されることも説明できる。さらに、生体内と生体外を分けるバリア機能、すなわちタイトジャンクションを持つ上皮シートが常に欠落なく維持される機構の存在を示すもので、学術的には基盤的な理解に大いに貢献する。