Center for Cell Biology and Cancer Research, Albany Medical College, Albany, NY 12208, USA.
Exp Cell Res. 2011 Apr 1;317(6):812-22. doi: 10.1016/j.yexcr.2010.12.002. Epub 2010 Dec 10.
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.
Arp2/3 复合物是肌动蛋白聚合的核酶，定位于迁移细胞的前沿突起中。目前尚不清楚该复合物如何靶向突起，以及其定位是否具有功能重要性。我们之前的研究表明，该复合物亚基的 mRNA 定位于成纤维细胞的突起中，这表明存在一种将复合物靶向突起的机制。我们在此介绍的数据表明，Arp2/3 复合物 mRNA 定位在细胞定向迁移中具有重要意义。利用 Dia1 mRNA 靶向核周内质网的新机制，我们将编码 Arp2/3 复合物亚基的 Arp2 mRNA 重定向到成纤维细胞的核周区域。单独敲低 Arp2 会导致复合物大量减少，并导致突起变窄、随机细胞迁移速度增加和方向丧失。用定位在突起的 Arp2 mRNA 进行拯救恢复了正常的细胞迁移行为，而用定位错误的 Arp2 mRNA 进行拯救则无法恢复速度和方向。这些结果表明，Arp2/3 复合物 mRNAs 在前沿突起中的定位对于细胞的定向迁移具有功能重要性。
