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Open AccessArticle

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

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
Friedrich-Miescher Institute for Biomedical Research, Maulbeerstr. 66, 4058 Basel, Switzerland
Institute of Experimental and Clinical Pharmakology and Toxicology, Faculty of Medicine, University of Freiburg, Alberstrasse 25, 79104 Freiburg, Germany
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;
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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