Division of Cell Biology and Molecular Medicine, Institute for Molecular Bioscience, The University of Queensland St. Lucia, Brisbane, QLD 4072, Australia.
Mechanobiology Institute of Singapore, National University of Singapore, Singapore 117411, Singapore.
Cell Rep. 2017 Mar 21;18(12):2854-2867. doi: 10.1016/j.celrep.2017.02.078.
Formins are a diverse class of actin regulators that influence filament dynamics and organization. Several formins have been identified at epithelial adherens junctions, but their functional impact remains incompletely understood. Here, we tested the hypothesis that formins might affect epithelial interactions through junctional contractility. We focused on mDia1, which was recruited to the zonula adherens (ZA) of established Caco-2 monolayers in response to E-cadherin and RhoA. mDia1 was necessary for contractility at the ZA, measured by assays that include a FRET-based sensor that reports molecular-level tension across αE-catenin. This reflected a role in reorganizing F-actin networks to form stable bundles that resisted myosin-induced stress. Finally, we found that the impact of mDia1 ramified beyond adherens junctions to stabilize tight junctions and maintain the epithelial permeability barrier. Therefore, control of tissue barrier function constitutes a pathway for cadherin-based contractility to contribute to the physiology of established epithelia.
成核因子是一类能够影响肌动蛋白丝动态和组织的肌动蛋白调节因子。已有多种成核因子在细胞连接处被鉴定，但它们的功能影响仍不完全清楚。在这里，我们测试了一个假设，即成核因子可能通过连接收缩来影响上皮细胞的相互作用。我们重点研究了 mDia1，它在 E-钙黏蛋白和 RhoA 的作用下被招募到已建立的 Caco-2 单层细胞的黏附连接（ZA）。mDia1 对于 ZA 的收缩是必需的，这可以通过 FRET 基传感器来测量，该传感器报告跨 αE-连环蛋白的分子水平张力。这反映了它在重新组织 F-肌动蛋白网络以形成抵抗肌球蛋白诱导的应力的稳定束中的作用。最后，我们发现 mDia1 的影响不仅仅局限于黏附连接，还可以稳定紧密连接并维持上皮通透性屏障。因此，组织屏障功能的控制构成了基于钙黏蛋白的收缩对已建立的上皮组织生理学的贡献途径。
