Laboratory of Molecular Biology, Graduate School of Agricultural Science, Tohoku University, Sendai 980-0845, Japan.
Terahertz Sensing and Imaging Research Team, RIKEN Center for Advanced Photonics, Sendai 980-0845, Japan.
Cells. 2020 Mar 19;9(3):758. doi: 10.3390/cells9030758.
The crosstalk between actin and actin-related proteins (Arps), namely Arp2 and Arp3, plays a central role in facilitating actin polymerization in the cytoplasm and also in the nucleus. Nuclear F-actin is required for transcriptional regulation, double-strand break repair, and nuclear organization. The formation of nuclear F-actin is highly dynamic, suggesting the involvement of positive and negative regulators for nuclear actin polymerization. While actin assembly factors for nuclear F-actin have been recently described, information about inhibitory factors is still limited. The actin-related protein Arp4 which is predominantly localized in the nucleus, has been previously identified as an integral subunit of multiple chromatin modulation complexes, where it forms a heterodimer with monomeric actin. Therefore, we tested whether Arp4 functions as a suppressor of nuclear F-actin formation. The knockdown of Arp4 (Arp4 KD) led to an increase in nuclear F-actin formation in NIH3T3 cells, and purified Arp4 potently inhibited F-actin formation in mouse nuclei transplanted into oocytes. Consistently, Arp4 KD facilitated F-actin-inducible gene expression (e.g., ) and DNA damage repair. Our results suggest that Arp4 has a critical role in the formation and functions of nuclear F-actin.
肌动蛋白和肌动蛋白相关蛋白（Arp）之间的串扰，即 Arp2 和 Arp3，在促进细胞质和细胞核中肌动蛋白聚合中起着核心作用。核 F-肌动蛋白对于转录调控、双链断裂修复和核组织是必需的。核 F-肌动蛋白的形成是高度动态的，这表明核肌动蛋白聚合涉及正向和负向调节剂。虽然最近已经描述了核 F-肌动蛋白的肌动蛋白组装因子，但关于抑制因子的信息仍然有限。Arp4 是一种主要定位于核内的肌动蛋白相关蛋白，先前已被鉴定为多个染色质调节复合物的完整亚基，在复合物中它与单体肌动蛋白形成异二聚体。因此，我们测试了 Arp4 是否作为核 F-肌动蛋白形成的抑制剂发挥作用。Arp4 的敲低（Arp4 KD）导致 NIH3T3 细胞中核 F-肌动蛋白的形成增加，并且纯化的 Arp4 可强烈抑制移植到卵母细胞中的小鼠核中的 F-肌动蛋白形成。一致地，Arp4 KD 促进了 F-肌动蛋白诱导的基因表达（例如，）和 DNA 损伤修复。我们的结果表明，Arp4 在核 F-肌动蛋白的形成和功能中起着关键作用。
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