Department of Anatomy and Structural Biology, Albert Einstein College of Medicine, Bronx, New York 10461, USA.
Genes Dev. 2012 Sep 1;26(17):1885-90. doi: 10.1101/gad.190413.112.
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 β-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 β-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.
定向细胞运动是发育、伤口愈合和转移等生物学现象的基础。已经表明，基质附着通过将细胞的细胞骨架与力的产生偶联来介导运动。然而，细胞方向的持久性是如何得到促进的还不清楚。我们表明，mRNA 定位在这个过程中起着重要作用，但作用机制尚不清楚。在这项研究中，我们表明 zipcode 结合蛋白 1 将 β-肌动蛋白 mRNA 运输到焦点附着区室，在那里停留数分钟，这表明通过在附着点和新合成的肌动蛋白丝之间形成稳定的连接，将其定位与运动联系起来的一种方法。为了证明这一点，我们开发了一种评估β-肌动蛋白 mRNA 和蛋白质定位的功能后果的方法，即将 mRNA tether 到特定的位置——在这种情况下，是焦点附着复合物。由于现在可以将任何 mRNA 及其同源蛋白强制引导到细胞中的特定位置，因此这种方法将对细胞生物学产生重大影响。这将揭示局部蛋白翻译在各种细胞过程中的重要性。
