Localization of all seven messenger RNAs for the actin-polymerization nucleator Arp2/3 complex in the protrusions of fibroblasts

Localization of all seven messenger RNAs for the actin-polymerization nucleator Arp2/3 complex in the protrusions of fibroblasts
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DOI:
10.1242/jcs.02371
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发表时间:
2005-06-01
影响因子:
4
通讯作者:
Liu, G
Liu, G
中科院分区:
生物学2区
文献类型:
--
作者:
Mingle, LA;Okuhama, NN;Liu, G

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肌动蛋白相关蛋白2/3(Arp 2/3)复合物是一种重要的肌动蛋白聚合成核剂,定位于迁移细胞的主要突起。然而,多蛋白复合物如何靶向突起仍然未知。在这里,我们证明了Arp 2/3复合物的七个亚基的mRNA定位于成纤维细胞的突起,支持Arp 2/3复合物通过mRNA定位靶向其功能位点的假设。从培养基中耗尽血清抑制Arp 2/3复合物mRNA定位到突起,而血清刺激导致30分钟内显著的mRNA定位。血清的影响表明,Arp 2/3复合物mRNA定位是细胞对细胞外刺激的反应。Arp 2/3复合体mRNA的定位依赖于肌动蛋白丝和微管,因为细胞骨架系统的破坏(分别用细胞松弛素D和秋水仙素)抑制了所有7个亚基mRNA的定位。此外,肌球蛋白抑制剂显着抑制Arp 2 mRNA在鸡胚成纤维细胞的定位,表明肌球蛋白运动依赖机制Arp 2/3复合物mRNA的定位。
The actin-related protein 2/3 (Arp2/3) complex is a crucial actin polymerization nucleator and is localized to the leading protrusions of migrating cells. However, how the multiprotein complex is targeted to the protrusions remains unknown. Here, we demonstrate that mRNAs for the seven subunits of the Arp2/3 complex are localized to the protrusions in fibroblasts, supporting a hypothesis that the Arp2/3 complex is targeted to its site of function by mRNA localization. Depletion of serum from culture medium inhibits Arp2/3-complex mRNA localization to the protrusion, whereas serum stimulation leads to significant mRNA localization within 30 minutes. The effect of serum suggests that Arp2/3-complex mRNA localization is a cellular response to extracellular stimuli. The localization of the Arp2/3 complex mRNAs is dependent on both actin filaments and microtubules, because disruption of either cytoskeletal system (with cytochalasin D and colchicine, respectively) inhibited the localization of all seven subunit mRNAs. In addition, myosin inhibitors significantly inhibit Arp2 mRNA localization in chicken embryo fibroblasts, suggesting a myosin motor dependent mechanism for Arp2/3-complex mRNA localization.