Faculty of Biology, Medicine and Health, University of Manchester, Manchester, M13 9PT, U.K.
Essays Biochem. 2019 Oct 31;63(5):595-606. doi: 10.1042/EBC20190009.
Cell migration is a fundamental biological process involved in tissue formation and homeostasis. The correct polarization of motile cells is critical to ensure directed movement, and is orchestrated by many intrinsic and extrinsic factors. Of these, the subcellular distribution of mRNAs and the consequent spatial control of translation are key modulators of cell polarity. mRNA transport is dependent on cis-regulatory elements within transcripts, which are recognized by trans-acting proteins that ensure the efficient delivery of certain messages to the leading edge of migrating cells. At their destination, translation of localized mRNAs then participates in regional cellular responses underlying cell motility. In this review, we summarize the key findings that established mRNA targetting as a critical driver of cell migration and how the characterization of polarized mRNAs in motile cells has been expanded from just a few species to hundreds of transcripts. We also describe the molecular control of mRNA trafficking, subsequent mechanisms of local protein synthesis and how these ultimately regulate cell polarity during migration.
细胞迁移是参与组织形成和动态平衡的基本生物学过程。运动细胞的正确极化对于确保定向运动至关重要,并且受到许多内在和外在因素的协调。在这些因素中,mRNA 的亚细胞分布和随之而来的翻译空间控制是细胞极性的关键调节剂。mRNA 运输依赖于转录本中的顺式调节元件,这些元件被反式作用蛋白识别,以确保某些信息有效地递送到迁移细胞的前缘。在它们的目的地,局部化的 mRNA 的翻译然后参与细胞运动下的区域细胞反应。在这篇综述中,我们总结了确立 mRNA 靶向作为细胞迁移关键驱动因素的关键发现,以及如何将运动细胞中极化 mRNA 的特征从少数几种扩展到数百种转录物。我们还描述了 mRNA 运输的分子控制、随后的局部蛋白质合成机制以及它们如何最终在迁移过程中调节细胞极性。