Actin flow-dependent and -independent force transmission through integrins
Actin flow-dependent and -independent force transmission through integrins
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DOI：
10.1073/pnas.2010292117
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发表时间：
2020-12-22
影响因子：
11.1
通讯作者：
Schwartz, Martin A.
中科院分区：
文献类型：
--
作者：
Driscoll, Tristan P.;Ahn, Sang Joon;Schwartz, Martin A.
整合素依赖性粘附介导细胞和细胞外基质之间的力和信息的相互交换。这些效应归因于“焦点粘附离合器”，其中移动的肌动蛋白丝通过动态蛋白质相互作用将力传递给整合素。为了阐明这些过程，我们测量了肌动蛋白所受的力和肌动蛋白的流速。在小的板足粘连中，对talin施加的力与肌动蛋白流动相关，而在远离细胞边缘的大粘连中，talin张力主要与流动无关。刚性衬底将力传递转向与流动无关的机制。流动依赖的力传递需要talin的c端肌动蛋白结合位点ABS3，而不需要血管蛋白。不依赖流动的力转移最初需要血毒蛋白，后来需要中央肌动蛋白结合位点ABS2。因此，整合素的力传递不是通过连续的离合器发生的，而是通过一系列由不同蛋白质相互作用介导的离散状态发生的，它们的比例由底物刚度调节。
Integrin-dependent adhesions mediate reciprocal exchange of force and information between the cell and the extracellular matrix. These effects are attributed to the "focal adhesion clutch," in which moving actin filaments transmit force to integrins via dynamic protein interactions. To elucidate these processes, we measured force on talin together with actin flow speed. While force on talin in small lamellipodial adhesions correlated with actin flow, talin tension in large adhesions further from the cell edge was mainly flow-independent. Stiff substrates shifted force transfer toward the flow-independent mechanism. Flow-dependent force transfer required talin's C-terminal actin binding site, ABS3, but not vinculin. Flow-independent force transfer initially required vinculin and at later times the central actin binding site, ABS2. Force transfer through integrins thus occurs not through a continuous clutch but through a series of discrete states mediated by distinct protein interactions, with their ratio modulated by substrate stiffness.