Talin tension sensor reveals novel features of focal adhesion force transmission and mechanosensitivity.
Talin tension sensor reveals novel features of focal adhesion force transmission and mechanosensitivity.
复制标题
塔林张力传感器揭示了局灶性粘附力传递和机械敏感性的新特征。
DOI：
10.1083/jcb.201510012
复制
发表时间：
2016-05-09
期刊：
影响因子：
--
通讯作者：
Schwartz MA
中科院分区：
文献类型：
--
作者：
Kumar A;Ouyang M;Van den Dries K;McGhee EJ;Tanaka K;Anderson MD;Groisman A;Goult BT;Anderson KI;Schwartz MA
细胞骨架衔接蛋白talin在连接整合素与肌动蛋白细胞骨架的粘附结构中起着重要作用。在这项工作中，Kumar等人使用一种新型talin传感器来测量talin张力，并提供了对粘着力传递和机械敏感性的见解。整合素依赖性粘连是机械敏感性结构，其中塔林蛋白通过募集黏着斑蛋白直接或间接介导与肌动蛋白丝的连接。在这里，我们报告的塔林张力传感器的开发和验证。我们发现局灶性粘连中的塔林处于张力下，外周粘连中的张力高于中央粘连。黏着斑蛋白增加了talin上的张力，并且主要依赖于杆结构域中间的肌动蛋白结合位点2（ABS2），而不是远C末端的ABS3。与黏着斑蛋白不同，talin在软基质上的张力较低。中央和外周粘连之间的差异需要ABS 3，而不是黏着斑蛋白或ABS 2。然而，通过talin的不同刚度感测需要ABS 2，而不需要黏着斑蛋白或ABS 3。这些结果表明，中央与外周粘连必须组织和调节不同，ABS2和ABS3在空间变化和刚度传感有不同的功能。总的来说，这些结果揭示了新的光talin功能和约束模型的细胞机械传感。
The cytoskeletal adapter protein talin plays a prominent role in adhesive structures connecting integrins to the actin cytoskeleton. In this work, Kumar et al. use a novel talin sensor to measure talin tension and provide insights into focal adhesion force transmission and mechanosensitivity. Integrin-dependent adhesions are mechanosensitive structures in which talin mediates a linkage to actin filaments either directly or indirectly by recruiting vinculin. Here, we report the development and validation of a talin tension sensor. We find that talin in focal adhesions is under tension, which is higher in peripheral than central adhesions. Tension on talin is increased by vinculin and depends mainly on actin-binding site 2 (ABS2) within the middle of the rod domain, rather than ABS3 at the far C terminus. Unlike vinculin, talin is under lower tension on soft substrates. The difference between central and peripheral adhesions requires ABS3 but not vinculin or ABS2. However, differential stiffness sensing by talin requires ABS2 but not vinculin or ABS3. These results indicate that central versus peripheral adhesions must be organized and regulated differently, and that ABS2 and ABS3 have distinct functions in spatial variations and stiffness sensing. Overall, these results shed new light on talin function and constrain models for cellular mechanosensing.