Integrins β1 and β3 exhibit distinct dynamic nanoscale organizations inside focal adhesions
Integrins β1 and β3 exhibit distinct dynamic nanoscale organizations inside focal adhesions
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DOI：
10.1038/ncb2588
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发表时间：
2012-10-01
影响因子：
21.3
通讯作者：
Giannone, Gregory
中科院分区：
文献类型：
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作者：
Rossier, Olivier;Octeau, Vivien;Giannone, Gregory
粘着斑中的整合素介导细胞与细胞外基质的粘附和力传递，对细胞运动、增殖和分化至关重要。同时存在于FA中的不同的纤连蛋白结合整合素执行不同的功能。然而，整合素动力学如何控制生化和生物力学过程中的脂肪酸仍然是难以捉摸的。使用单蛋白跟踪和超分辨率成像，我们揭示了整合素和talin在FA内的动态纳米组织。整合素通过自由扩散和固定循环驻留在FA中。整合素活化促进固定化，通过同时连接到纤连蛋白和肌动蛋白结合蛋白而稳定在FA中。Talin直接从细胞质中募集到FA中，而没有膜自由扩散，限制了整合素固定到FA。固定化的β（3）-整联蛋白在FA中富集和固定，而固定化的β（1）-整联蛋白富集较少并表现出向后运动。塔林是丰富的，主要是固定的，但也表现出向后运动的脂肪酸，与稳定的连接与β-整联蛋白。因此，肌动蛋白运动到纤连蛋白的差异传递通过FA内的特异性整合素发生。
Integrins in focal adhesions (FAs) mediate adhesion and force transmission to extracellular matrices essential for cell motility, proliferation and differentiation. Different fibronectin-binding integrins, simultaneously present in FAs, perform distinct functions. Yet, how integrin dynamics control biochemical and biomechanical processes in FAs is still elusive. Using single-protein tracking and super-resolution imaging we revealed the dynamic nano-organizations of integrins and talin inside FAs. Integrins reside in FAs through free-diffusion and immobilization cycles. Integrin activation promotes immobilization, stabilized in FAs by simultaneous connection to fibronectin and actin-binding proteins. Talin is recruited in FAs directly from the cytosol without membrane free-diffusion, restricting integrin immobilization to FAs. Immobilized beta(3)-integrins are enriched and stationary within FAs, whereas immobilized beta(1)-integrins are less enriched and exhibit rearward movements. Talin is enriched and mainly stationary, but also exhibited rearward movements in FAs, consistent with stable connections with both beta-integrins. Thus, differential transmission of actin motion to fibronectin occurs through specific integrins within FAs.