β-Actin mRNA compartmentalization enhances focal adhesion stability and directs cell migration
β-Actin mRNA compartmentalization enhances focal adhesion stability and directs cell migration
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DOI：
10.1101/gad.190413.112
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发表时间：
2012-09-01
影响因子：
10.5
通讯作者：
Singer, Robert H.
中科院分区：
文献类型：
--
作者：
Katz, Zachary B.;Wells, Amber L.;Singer, Robert H.
定向细胞运动是生物学现象如发育、伤口愈合和转移的基础。它已被证明，基板附件介导的运动耦合细胞的细胞骨架与力的产生。然而，目前还不清楚细胞方向性的持续性是如何促进的。我们发现，mRNA定位在这一过程中起着重要的作用，但其作用机制仍然是未知的。在这项研究中，我们表明，邮编结合蛋白1运输β-肌动蛋白mRNA的粘着斑区室，在那里它停留了几分钟，这表明了一种方法，通过形成稳定的连接粘连和新合成的肌动蛋白丝之间的运动与其本地化。为了证明这一点，我们开发了一种方法来评估β-肌动蛋白mRNA和蛋白定位的功能后果，通过将mRNA拴在一个特定的位置，在这种情况下，粘着斑复合物。这种方法将对细胞生物学产生重大影响，因为现在可以强制将任何mRNA及其同源蛋白质引导到细胞中的特定位置。这将揭示定位蛋白质翻译对各种细胞过程的重要性。
Directed cell motility is at the basis of biological phenomena such as development, wound healing, and metastasis. It has been shown that substrate attachments mediate motility by coupling the cell's cytoskeleton with force generation. However, it has been unclear how the persistence of cell directionality is facilitated. We show that mRNA localization plays an important role in this process, but the mechanism of action is still unknown. In this study, we show that the zipcode-binding protein 1 transports beta-actin mRNA to the focal adhesion compartment, where it dwells for minutes, suggesting a means for associating its localization with motility through the formation of stable connections between adhesions and newly synthesized actin filaments. In order to demonstrate this, we developed an approach for assessing the functional consequences of beta-actin mRNA and protein localization by tethering the mRNA to a specific location-in this case, the focal adhesion complex. This approach will have a significant impact on cell biology because it is now possible to forcibly direct any mRNA and its cognate protein to specific locations in the cell. This will reveal the importance of localized protein translation on various cellular processes.