细胞-细胞机械转导调节组织发育和稳态。α-连环蛋白,粘附连接的核心部件,通过募集vinculin和转导影响细胞行为的信号,充当张力传感器和换能器。α-连环蛋白/黏珠蛋白复合物介导的机械转导调节多种途径,例如河马途径。然而,它们与细胞连接处基于α-catenin的张力传感器的关联仍未完全解决。这里,我们发现TRIP6/LATS1复合物与α-catenin/vinculin共定位在双细胞连接(BCJs)和三细胞连接(TCJs)。TRIP6/LATS1复合物在TCJ和BCJ中的定位需要ROCK1和α-catenin。用细胞松弛素B治疗,Y-27632和blebbistatin均损害了TRIP6/LATS1的BCJ和TCJ连接定位,表明TRIP6/LATS1的连接定位是机械敏感性的。α-连环蛋白/vinculin/TRIP6/LATS1复合物强烈定位在TCJ上,并在BCJ上表现出不连续的纽扣状图案。此外,我们开发并验证了基于α-catenin/vinculinBiFC的机械传感器,该传感器与TRIP6/LATS1在BCJs和TCJs上共定位。机械传感器在BCJ处表现出不连续的分布和运动信号。总的来说,我们的研究表明,TRIP6和LATS1是张力传感器的新型组合物,连同α-连环蛋白/黏珠蛋白的核心复合物,在BCJ和TCJ。
Cell-cell mechanotransduction regulates tissue development and homeostasis. α-catenin, the core component of adherens junctions, functions as a tension sensor and transducer by recruiting
vinculin and transducing signals that influence cell behaviors. α-catenin/
vinculin complex-mediated mechanotransduction regulates multiple pathways, such as Hippo pathway. However, their associations with the α-catenin-based tension sensors at cell junctions are still not fully addressed. Here, we uncovered the TRIP6/LATS1 complex co-localizes with α-catenin/
vinculin at both bicellular junctions (BCJs) and tricellular junctions (TCJs). The localization of TRIP6/LATS1 complex to both TCJs and BCJs requires ROCK1 and α-catenin. Treatment by cytochalasin B, Y-27632 and blebbistatin all impaired the BCJ and TCJ junctional localization of TRIP6/LATS1, indicating that the junctional localization of TRIP6/LATS1 is mechanosensitive. The α-catenin/vinculin/TRIP6/LATS1 complex strongly localized to TCJs and exhibited a discontinuous button-like pattern on BCJs. Additionally, we developed and validated an α-catenin/
vinculin BiFC-based mechanosensor that co-localizes with TRIP6/LATS1 at BCJs and TCJs. The mechanosensor exhibited a discontinuous distribution and motile signals at BCJs. Overall, our study revealed that TRIP6 and LATS1 are novel compositions of the tension sensor, together with the core complex of α-catenin/
vinculin, at both the BCJs and TCJs.