Data from: HMP-1/α-catenin promotes junctional mechanical integrity during morphogenesis

Adherens junctions (AJs) are key structures regulating tissue integrity and maintaining adhesion between cells. During morphogenesis, junctional proteins cooperate closely with the actomyosin network to drive cell movement and shape changes. How the junctions integrate the mechanical forces in space and in time during an in vivo morphogenetic event is still largely unknown, due to a lack of quantitative data. To address this issue, we inserted a functional Fluorescence Resonance Energy Transfer (FRET)-based force biosensor within HMP-1/a-catenin of Caenorhabditis elegans. We find that the tension exerted on HMP-1 has a cell-specific distribution, is actomyosin-dependent, but is regulated differently from the tension on the actin cortex during embryonic elongation. By using time-lapse analysis of mutants and tissue-specific rescue experiments, we confirm the role of VAB-9/Claudin as an actin bundle anchor. Nevertheless, the tension exerted on HMP-1 did not increase in the absence of VAB-9/Claudin, suggesting that HMP-1 activity is not upregulated to compensate for loss of VAB-9. Our data indicate that HMP-1 does not modulate HMR-1/E-cadherin turnover, is required to recruit junctional actin but not stress fiber-like actin bundles. Altogether, our data suggest that HMP-1/a-catenin acts to promote the mechanical integrity of adherens junctions.

黏着连接（Adherens junctions, AJs）是调控组织完整性、维持细胞间黏附的关键结构。在形态发生过程中，连接蛋白与肌动球蛋白网络紧密协作，驱动细胞运动与形态改变。受限于定量数据的匮乏，目前人们对体内形态发生事件中黏着连接如何在时空维度整合机械力这一问题仍未得到充分阐明。为解决这一问题，我们将基于荧光共振能量转移（Fluorescence Resonance Energy Transfer, FRET）的功能性力生物传感器插入到秀丽隐杆线虫（Caenorhabditis elegans）的HMP-1/α-连环蛋白中。我们发现，作用于HMP-1的张力具有细胞特异性分布，且依赖于肌动球蛋白网络，但在胚胎伸长过程中，其调控机制与肌动皮层上的张力调控机制存在差异。通过对突变体开展延时成像分析与组织特异性挽救实验，我们证实VAB-9/紧密连接蛋白（Claudin）可作为肌动蛋白束锚定蛋白。然而，在缺失VAB-9/紧密连接蛋白的情况下，作用于HMP-1的张力并未升高，这表明HMP-1的活性并未上调以弥补VAB-9的缺失。我们的研究数据显示，HMP-1并不会调控HMR-1/上皮钙黏蛋白（E-cadherin）的周转，且仅参与招募连接相关肌动蛋白，而非应力纤维样肌动蛋白束。综上，我们的研究数据表明，HMP-1/α-连环蛋白的作用是增强黏着连接的机械完整性。