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

Shota Yamazaki, Christian Gerhold, Koji Yamamoto, Yuya Ueno, Robert Grosse, Kei Miyamoto, Masahiko Harata

    Research output: Contribution to journalArticlepeer-review

    6 Citations (Scopus)

    Abstract

    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.

    Original languageEnglish
    JournalCells
    Volume9
    Issue number3
    DOIs
    Publication statusPublished - 2020 Mar 19

    Keywords

    • actin-related protein
    • epigenetics
    • nuclear actin
    • nuclear architecture
    • nucleoskeleton

    ASJC Scopus subject areas

    • Medicine(all)

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