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Open AccessArticle

The Actin-Family Protein Arp4 Is a Novel Suppressor for the Formation and Functions of Nuclear F-Actin

1
Laboratory of Molecular Biology, Graduate School of Agricultural Science, Tohoku University, Sendai 980-0845, Japan
2
Terahertz Sensing and Imaging Research Team, RIKEN Center for Advanced Photonics, Sendai 980-0845, Japan
3
Friedrich-Miescher Institute for Biomedical Research, Maulbeerstr. 66, 4058 Basel, Switzerland
4
Institute of Experimental and Clinical Pharmakology and Toxicology, Faculty of Medicine, University of Freiburg, Alberstrasse 25, 79104 Freiburg, Germany
5
Laboratory of Molecular Developmental Biology, Faculty of Biology-Oriented Science and Technology, Kindai University, Wakayama 649-6493, Japan
*
Authors to whom correspondence should be addressed.
Cells 2020, 9(3), 758; https://doi.org/10.3390/cells9030758
Received: 20 January 2020 / Revised: 6 March 2020 / Accepted: 17 March 2020 / Published: 19 March 2020
(This article belongs to the Special Issue Nuclear Architecture, Lipids, and Phase Separation)
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. View Full-Text
Keywords: nuclear architecture; nuclear actin; actin-related protein; nucleoskeleton; epigenetics nuclear architecture; nuclear actin; actin-related protein; nucleoskeleton; epigenetics
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Yamazaki, S.; Gerhold, C.; Yamamoto, K.; Ueno, Y.; Grosse, R.; Miyamoto, K.; Harata, M. The Actin-Family Protein Arp4 Is a Novel Suppressor for the Formation and Functions of Nuclear F-Actin. Cells 2020, 9, 758.

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