The fibronectin synergy site re-enforces cell adhesion and mediates a crosstalk between integrin classes.
The fibronectin synergy site re-enforces cell adhesion and mediates a crosstalk between integrin classes.
复制标题
纤连蛋白协同部位重新启动细胞粘附并介导整联蛋白类之间的串扰。
DOI：
10.7554/elife.22264
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发表时间：
2017-01-16
期刊：
影响因子：
7.7
通讯作者：
Costell M
中科院分区：
文献类型：
--
作者：
Benito-Jardón M;Klapproth S;Gimeno-LLuch I;Petzold T;Bharadwaj M;Müller DJ;Zuchtriegel G;Reichel CA;Costell M
纤连蛋白（FN）是一种主要的细胞外基质成分，通过α5β1、αIIbβ3和α v类整合素与RGD基序的结合来实现整合素介导的细胞粘附。α5和αIIb的另一个连接是靠近RGD基序的协同位点。我们报告说，功能失调的FN协同基序（Fn 1 syn/syn）的小鼠患有令人惊讶的轻微血小板粘附和出血缺陷，由于血管损伤后延迟血栓形成。β3整联蛋白的额外损失显著增加眼睑，并严重损害血管系统的平滑肌细胞覆盖，导致胚胎死亡。基于细胞的研究表明，协同位点对于α5β1与RGD的初始接触是不重要的，但对于重新加强α5β1/αIIbβ3与FN的结合是必需的。我们的研究结果表明，当外力超过一定的阈值或αvβ3整合素水平下降到临界水平以下时，FN协同位点发挥关键作用。DOI：http://dx.doi.org/10.7554/eLife.22264.001网站
Fibronectin (FN), a major extracellular matrix component, enables integrin-mediated cell adhesion via binding of α5β1, αIIbβ3 and αv-class integrins to an RGD-motif. An additional linkage for α5 and αIIb is the synergy site located in close proximity to the RGD motif. We report that mice with a dysfunctional FN-synergy motif (Fn1syn/syn) suffer from surprisingly mild platelet adhesion and bleeding defects due to delayed thrombus formation after vessel injury. Additional loss of β3 integrins dramatically aggravates the bleedings and severely compromises smooth muscle cell coverage of the vasculature leading to embryonic lethality. Cell-based studies revealed that the synergy site is dispensable for the initial contact of α5β1 with the RGD, but essential to re-enforce the binding of α5β1/αIIbβ3 to FN. Our findings demonstrate a critical role for the FN synergy site when external forces exceed a certain threshold or when αvβ3 integrin levels decrease below a critical level. DOI: http://dx.doi.org/10.7554/eLife.22264.001