Sala Stefano, Chandrasekar Shreya, Troughton Lee, Wu Huini, Beach Jordan R, Oakes Patrick W
bioRxiv. 2025 Jul 17:2025.07.16.665189. doi: 10.1101/2025.07.16.665189.
Mechanotransduction is fundamental to cell signaling and depends on force-sensitive adhesion proteins. How these proteins differentiate and integrate their responses to tension remains an open question. We show mechanosensitive LIM domain proteins like zyxin detect global adhesion tension by recognizing strained actin within these structures. In sharp contrast, vinculin localization and intramolecular tension remain unchanged, despite vinculin's well-documented role in mechanotransduction. This reveals a stark disconnect between molecular tension and global tension in adhesions. We further show tension-dependent localization is specific to LIM domain proteins that recognize strained actin and extends to LIM proteins at cell-cell junctions, suggesting a common mechanotransduction mechanism. Finally, we show zyxin's tension-dependent adhesion localization stabilizes actin and recruits VASP to promote stress fiber polymerization, identical to its role in stress fiber repair. Our findings reveal a fundamental role for LIM domain protein force-sensing in adhesions and highlight the non-linear connection between molecular and global tension.
机械转导是细胞信号传导的基础，并且依赖于力敏感粘附蛋白。这些蛋白如何区分并整合它们对张力的反应仍是一个悬而未决的问题。我们发现，像桩蛋白这样的机械敏感LIM结构域蛋白通过识别这些结构内的应变肌动蛋白来检测整体粘附张力。与之形成鲜明对比的是，尽管纽蛋白在机械转导中的作用已得到充分证明，但其定位和分子内张力却保持不变。这揭示了粘附分子中的分子张力与整体张力之间存在明显脱节。我们进一步表明，张力依赖性定位是识别应变肌动蛋白的LIM结构域蛋白所特有的，并且延伸到细胞间连接的LIM蛋白，这表明存在一种共同的机械转导机制。最后，我们表明桩蛋白的张力依赖性粘附定位可稳定肌动蛋白并募集vasodilator-stimulated phosphoprotein（VASP）以促进应力纤维聚合，这与其在应力纤维修复中的作用相同。我们的研究结果揭示了LIM结构域蛋白力感知在粘附中的基本作用，并突出了分子张力与整体张力之间的非线性联系。
