Windgasse Lukas, Grashoff Carsten
University of Münster, Institute of Integrative Cell Biology and Physiology, Münster, Germany.
Commun Biol. 2025 Sep 1;8(1):1325. doi: 10.1038/s42003-025-08785-3.
The formation and maintenance of epithelia is critical for animal development and survival. Central to epithelial integrity are cadherin-based complexes called adherens junctions (AJs), which form physically robust but inherently dynamic cell-cell adhesions. How AJs function at the molecular level remains incompletely understood because techniques to study the central AJ proteins within the dynamic adhesion structure are scarce. Using a conformation sensitive probe that is amenable to fluorescence lifetime and anisotropy imaging, we demonstrate that the maturation of AJs is accompanied by a conformational change in the actin-binding domain of α-catenin. The structural transition depends on the degree of junctional maturation and requires actin polymerisation, but it is insensitive to vinculin binding to α-catenin. These different conformational states correlate with distinct α-catenin mobilities, with α-catenin unexpectedly showing an overall increased protein turnover in mature AJs. Collectively, the data reveal that α-catenin undergoes a previously proposed C-terminal conformational transition during epidermal differentiation to form mechanically stable yet dynamic cell-cell adhesions.
上皮细胞的形成和维持对于动物的发育和生存至关重要。基于钙黏蛋白的复合物，即黏着连接（AJs），是上皮细胞完整性的核心，它们形成了物理上坚固但本质上动态的细胞间黏附。由于在动态黏附结构中研究核心AJ蛋白的技术匮乏，AJs在分子水平上的功能仍未完全被理解。使用一种适用于荧光寿命和各向异性成像的构象敏感探针，我们证明AJs的成熟伴随着α-连环蛋白肌动蛋白结合结构域的构象变化。这种结构转变取决于连接成熟的程度，并且需要肌动蛋白聚合，但它对纽蛋白与α-连环蛋白的结合不敏感。这些不同的构象状态与α-连环蛋白不同的迁移率相关，α-连环蛋白在成熟的AJs中意外地显示出整体蛋白质周转增加。总体而言，这些数据表明，α-连环蛋白在表皮分化过程中经历了先前提出的C端构象转变，以形成机械稳定但动态的细胞间黏附。
