F-and G-actin homeostasis regulates mechanosensitive actin nucleation by formins

Chiharu Higashida, Tai Kiuchi, Yushi Akiba, Hiroaki Mizuno, Masahiro Maruoka, Shuh Narumiya, Kensaku Mizuno, Naoki Watanabe

    Research output: Contribution to journalArticle

    65 Citations (Scopus)

    Abstract

    Physical force evokes rearrangement of the actin cytoskeleton. Signalling pathways such as tyrosine kinases, stretch-activated Ca2+ channels and Rho GTPases are involved in force sensing. However, how signals are transduced to actin assembly remains obscure. Here we show mechanosensitive actin polymerization by formins (formin homology proteins). Cells overexpressing mDia1 increased the amount of F-actin on release of cell tension. Fluorescence single-molecule speckle microscopy revealed rapid induction of processive actin assembly by mDia1 on cell cortex deformation. mDia1 lacking the Rho-binding domain and other formins exhibited mechanosensitive actin nucleation, suggesting Rho-independent activation. Mechanosensitive actin nucleation by mDia1 required neither Ca2+ nor kinase signalling. Overexpressing LIM kinase abrogated the induction of processive mDia1. Furthermore, s-FDAPplus (sequential fluorescence decay after photoactivation) analysis revealed a rapid actin monomer increase on cell cortex deformation. Our direct visualization of the molecular behaviour reveals a mechanosensitive actin filament regeneration mechanism in which G-actin released by actin remodelling plays a pivotal role.

    Original languageEnglish
    Pages (from-to)395-405
    Number of pages11
    JournalNature cell biology
    Volume15
    Issue number4
    DOIs
    Publication statusPublished - 2013 Apr

    ASJC Scopus subject areas

    • Cell Biology

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  • Cite this

    Higashida, C., Kiuchi, T., Akiba, Y., Mizuno, H., Maruoka, M., Narumiya, S., Mizuno, K., & Watanabe, N. (2013). F-and G-actin homeostasis regulates mechanosensitive actin nucleation by formins. Nature cell biology, 15(4), 395-405. https://doi.org/10.1038/ncb2693