Pre-complexation of talin and vinculin without tension is required for efficient nascent adhesion maturation.
Pre-complexation of talin and vinculin without tension is required for efficient nascent adhesion maturation.
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DOI：
10.7554/elife.66151
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发表时间：
2021-03-30
期刊：
影响因子：
7.7
通讯作者：
Danuser G
中科院分区：
文献类型：
--
作者：
Han SJ;Azarova EV;Whitewood AJ;Bachir A;Guttierrez E;Groisman A;Horwitz AR;Goult BT;Dean KM;Danuser G
Talin和vinculin是机械敏感蛋白，早期被招募到基于整合素的新生粘连(NAS)中。在两个轮廓清晰的NA形成的上皮细胞系统中，我们发现这些分子同时招募到Nas亚类，成熟为局灶性粘连。在最小负荷下的初始募集后，纽蛋白在成熟的NAS中的积聚速度是未成熟的NAS的5倍，并且伴随着更快的牵引力增加。我们在talin中鉴定了R8结构域，它在没有负载的情况下暴露出一个纽蛋白结合位点(VBS)，这是NA成熟所必需的。R8结构域功能的中断减少了纽蛋白与Talin的无负荷结合，并降低了额外纽蛋白的募集速度。综上所述，这些数据表明，在与整合素机械结合之前同时招募talin和vinculin对于牵引力介导的talin的展开、暴露额外的VBSS、进一步招募vinculin以及最终NA成熟是必不可少的。
Talin and vinculin are mechanosensitive proteins that are recruited early to integrin-based nascent adhesions (NAs). In two epithelial cell systems with well-delineated NA formation, we find these molecules concurrently recruited to the subclass of NAs maturing to focal adhesions. After the initial recruitment under minimal load, vinculin accumulates in maturing NAs at a ~ fivefold higher rate than in non-maturing NAs, and is accompanied by a faster traction force increase. We identify the R8 domain in talin, which exposes a vinculin-binding-site (VBS) in the absence of load, as required for NA maturation. Disruption of R8 domain function reduces load-free vinculin binding to talin, and reduces the rate of additional vinculin recruitment. Taken together, these data show that the concurrent recruitment of talin and vinculin prior to mechanical engagement with integrins is essential for the traction-mediated unfolding of talin, exposure of additional VBSs, further recruitment of vinculin, and ultimately, NA maturation.