Vinculin controls focal adhesion formation by direct interactions with talin and actin.
Vinculin controls focal adhesion formation by direct interactions with talin and actin.
复制标题
DOI：
10.1083/jcb.200703036
复制
发表时间：
2007-12-03
期刊：
影响因子：
--
通讯作者：
Ballestrem C
中科院分区：
文献类型：
--
作者：
Humphries JD;Wang P;Streuli C;Geiger B;Humphries MJ;Ballestrem C
局灶性粘连（FAs）调节细胞迁移。与其许多潜在的结合伙伴，可以互连信号的脂肪酸。尽管黏着斑蛋白的结构特征很好，但其作用的分子机制仍不清楚。在这里，使用黏着斑蛋白突变体，我们分离黏着斑蛋白的头部和尾部区域到不同的功能域。我们表明，黏着斑蛋白头调节整合素的动力学和集群和尾巴调节机械力机械的联系。黏着斑蛋白结构的表达与未掩蔽的结合位点的头部和尾部区域诱导显着的FA的增长，这是由它们的直接相互作用与塔林介导的。这种相互作用导致活化的整合素聚集和整合素在FA中的停留时间增加。令人惊讶的是，由活性黏着斑蛋白构建体诱导的桩蛋白募集独立于其在黏着斑蛋白尾部的潜在结合位点而发生。然而，黏着斑蛋白尾部负责FA与肌动蛋白细胞骨架的功能性连接。我们提出了一个新的模型，解释了黏着斑蛋白如何编排脂肪酸。
Focal adhesions (FAs) regulate cell migration. Vinculin, with its many potential binding partners, can interconnect signals in FAs. Despite the well-characterized structure of vinculin, the molecular mechanisms underlying its action have remained unclear. Here, using vinculin mutants, we separate the vinculin head and tail regions into distinct functional domains. We show that the vinculin head regulates integrin dynamics and clustering and the tail regulates the link to the mechanotransduction force machinery. The expression of vinculin constructs with unmasked binding sites in the head and tail regions induces dramatic FA growth, which is mediated by their direct interaction with talin. This interaction leads to clustering of activated integrin and an increase in integrin residency time in FAs. Surprisingly, paxillin recruitment, induced by active vinculin constructs, occurs independently of its potential binding site in the vinculin tail. The vinculin tail, however, is responsible for the functional link of FAs to the actin cytoskeleton. We propose a new model that explains how vinculin orchestrates FAs.
登录
查看更多内容
影响因子：
56.9
作者：
Hu, Ke;Ji, Lin;Waterman-Storer, Clare M.
通讯作者：
Waterman-Storer, Clare M.
影响因子：
16
作者：
Janssen, MEW;Kim, E;Hanein, D
通讯作者：
Hanein, D
影响因子：
4.8
作者：
Chen, Hui;Choudhury, Dilshad M.;Craig, Susan W.
通讯作者：
Craig, Susan W.
影响因子：
4.8
作者：
Cohen, DM;Chen, H;Craig, SW
通讯作者：
Craig, SW
影响因子：
4.8
作者：
BAZZONI, G;SHIH, DT;HEMLER, ME
通讯作者：
HEMLER, ME