Mechanism underlying the association of actomyosin bundles with adherens junctions in epithelial cells

2022 Fiscal Year Final Research Report

• Project/Area Number: 20K15793
• Research Category: Grant-in-Aid for Early-Career Scientists
• Allocation Type: Multi-year Fund
• Review Section: Basic Section 44010:Cell biology-related
• Research Institution: The University of Tokushima
• Principal Investigator: SAKAKIBARA Shotaro 徳島大学, 大学院医歯薬学研究部(医学域), 助教 (80836396)
• Project Period (FY): 2020-04-01 – 2023-03-31
• Keywords: 細胞間接着 / アドヘレンスジャンクション / アクトミオシン束 / カドヘリン-カテニン複合体 / アファディン

Outline of Final Research Achievements

Actomyosin-undercoated adherens junctions are critical for epithelial cell integrity and remodeling. Actomyosin associates with adherens junctions through αE-catenin complexed with β-catenin and E-cadherin in vivo; however, in vitro biochemical studies in solution showed that αE-catenin complexed with β-catenin binds to F-actin less efficiently than αE-catenin that is not complexed with β-catenin. Although a "catch-bond model" partly explains this inconsistency, the mechanism for this inconsistency between the in vivo and in vitro results remains elusive. We herein demonstrate that afadin binds to αE-catenin complexed with β-catenin and enhances its F-actin-binding activity in a novel mechanism, eventually inducing the proper actomyosin organization through αE-catenin complexed with β-catenin and E-cadherin at adherens junctions.

Free Research Field

生化学、細胞生物学

Academic Significance and Societal Importance of the Research Achievements

上皮細胞は、隣り合う細胞同士が細胞間接着によって接着し、生体の内外を隔てる上皮シートを形成している。この上皮シートの破綻はさまざまな疾患の発症と進行に関わる。本研究成果を端緒として、AM束による上皮シートの機械的強度の維持とリモデリングを担うタンパク質-タンパク質相互作用のネットワークの解明が進むことで、新たな疾患バイオマーカーの開発や創薬標的の創出につながることが期待される。