The Actin-Family Protein Arp4 Is a Novel Suppressor for the Formation and Functions of Nuclear F-Actin
The Actin-Family Protein Arp4 Is a Novel Suppressor for the Formation and Functions of Nuclear F-Actin
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DOI：
10.3390/cells9030758
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发表时间：
2020-03
期刊：
影响因子：
6
通讯作者：
S. Yamazaki;C. Gerhold;Koji Yamamoto;Yuya Ueno;R. Grosse;Kei Miyamoto;M. Harata
中科院分区：
文献类型：
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作者：
S. Yamazaki;C. Gerhold;Koji Yamamoto;Yuya Ueno;R. Grosse;Kei Miyamoto;M. Harata
肌动蛋白和肌动蛋白相关蛋白（Arps），即Arp 2和Arp 3之间的串扰，在促进细胞质和细胞核中的肌动蛋白聚合中起着核心作用。核F-肌动蛋白是转录调控、双链断裂修复和核组织所必需的。核F-肌动蛋白的形成是高度动态的，这表明参与核肌动蛋白聚合的正和负调节剂。虽然最近已经描述了核F-肌动蛋白的肌动蛋白装配因子，但关于抑制因子的信息仍然有限。肌动蛋白相关蛋白Arp 4主要定位于细胞核中，先前已被鉴定为多染色质调节复合物的组成亚基，在那里它与单体肌动蛋白形成异二聚体。因此，我们测试了Arp 4是否作为核F-肌动蛋白形成的抑制因子发挥作用。敲低Arp 4（Arp 4 KD）导致NIH 3 T3细胞核中F-肌动蛋白形成增加，纯化的Arp 4有效地抑制移植到非洲爪蟾卵母细胞中的小鼠核中F-肌动蛋白的形成。一致地，Arp 4 KD促进F-肌动蛋白诱导的基因表达（例如，OCT 4）和DNA损伤修复。我们的研究结果表明，Arp 4在核F-肌动蛋白的形成和功能中具有关键作用。
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 Xenopus laevis oocytes. Consistently, Arp4 KD facilitated F-actin-inducible gene expression (e.g., OCT4) and DNA damage repair. Our results suggest that Arp4 has a critical role in the formation and functions of nuclear F-actin.