Mis-localization of Arp2 mRNA impairs persistence of directional cell migration.
Mis-localization of Arp2 mRNA impairs persistence of directional cell migration.
复制标题
Arp2 mRNA 的错误定位会损害定向细胞迁移的持久性。
DOI：
10.1016/j.yexcr.2010.12.002
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发表时间：
2011
影响因子：
3.7
通讯作者：
Liu,Gang
中科院分区：
文献类型：
--
作者：
Liao,Guoning;Simone,Brittany;Liu,Gang
Arp2/3 复合物是一种肌动蛋白聚合成核剂，位于迁移细胞的前导突起中。目前尚不清楚该复合物如何靶向突出物以及其定位是否具有重要的功能。我们之前证明，编码复合物亚基的 mRNA 位于成纤维细胞的突起中，这表明了一种将复合物靶向突起的机制。我们在这里提供的数据证明了 Arp2/3 复合物 mRNA 定位在定向细胞迁移中的重要性。利用 Dia1 mRNA 靶向核周内质网的新机制，我们将编码 Arp2（Arp2/3 复合体的一个亚基）的 mRNA 重定向到成纤维细胞的核周区域。单独敲除 Arp2 会导致复合物急剧减少，并导致狭窄的突起、随机细胞迁移速度增加和方向性丧失。使用突出定位的 Arp2 mRNA 进行救援可以恢复正常的细胞迁移行为，而使用错误定位的 Arp2 mRNA 进行救援则无法恢复速度和方向性。这些结果表明，Arp2/3 复合体 mRNA 在前导突起中的定位对于定向细胞迁移具有重要的功能。
Arp2/3 complex is an actin polymerization nucleator and localized in the leading protrusions of migrating cells. It has been unclear how this complex is targeted to the protrusions and whether its localization is functionally important. We previously demonstrated that mRNAs encoding for the subunits of the complex were localized in the protrusions of fibroblasts, suggesting a mechanism to target the complex to the protrusions. We here present data demonstrating the importance of Arp2/3 complex mRNA localization in directional cell migration. Using a novel mechanism by which Dia1 mRNA is targeted to the perinuclear endoplasmic reticulum, we redirected the mRNA encoding Arp2, a subunit of the Arp2/3 complex, to the perinuclear region in fibroblasts. Knockdown of Arp2 alone caused dramatic reduction of the complex and resulted in narrow protrusions, increased random cell migration speed and loss of directionality. Rescue with a protrusion-localizing Arp2 mRNA restored normal cell migration behavior, whereas rescue with a mis-localizing Arp2 mRNA failed to restore speed and directionality. These results demonstrate that localization of Arp2/3 complex mRNAs in the leading protrusions is functionally important for directional cell migration.