G-actin regulates rapid induction of actin nucleation by mDia1 to restore cellular actin polymers

Chiharu Higashida, Shiro Suetsugu, Takahiro Tsuji, James Monypenny, Shuh Narumiya, Naoki Watanabe

    Research output: Contribution to journalArticlepeer-review

    42 Citations (Scopus)

    Abstract

    mDia1 belongs to the formin family of proteins that share FH1 and FH2 domains. Although formins play a critical role in the formation of many actin-based cellular structures, the physiological regulation of formin-mediated actin assembly within the cell is still unknown. Here we show that cells possess an acute actin polymer restoration mechanism involving mDia1. By using single-molecule live-cell imaging, we found that several treatments including low-dose G-actin-sequestering drugs and unpolymerizable actin mutants activate mDia1 to initiate fast directional movement. The FH2 region, the core domain for actin nucleation, is sufficient to respond to latrunculin B (LatB) to increase its actin nucleation frequency. Simulation analysis revealed an unexpected paradoxical effect of LatB that leads to a several fold increase in free G-actin along with an increase in total G-actin. These results indicate that in cells, the actin nucleation frequency of mDia1 is enhanced not only by Rho, but also strongly through increased catalytic efficiency of the FH2 domain. Consistently, frequent actin nucleation by mDia1 was found around sites of vigorous actin disassembly. Another major actin nucleator, the Arp2/3 complex, was not affected by the G-actin increase induced by LatB. Taken together, we propose that transient accumulation of G-actin works as a cue to promote mDia1-catalyzed actin nucleation to execute rapid reassembly of actin filaments.

    Original languageEnglish
    Pages (from-to)3403-3412
    Number of pages10
    JournalJournal of cell science
    Volume121
    Issue number20
    DOIs
    Publication statusPublished - 2008 Oct 15

    Keywords

    • Actin nucleation
    • Formin
    • G-actin
    • Rho
    • mDia

    ASJC Scopus subject areas

    • Cell Biology

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