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First published online 30 September 2008
doi: 10.1242/jcs.030940

Journal of Cell Science 121, 3403-3412 (2008)
Published by The Company of Biologists 2008
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Research Article

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

Chiharu Higashida1, Shiro Suetsugu2,3, Takahiro Tsuji1, James Monypenny1, Shuh Narumiya1 and Naoki Watanabe1,*

1 Department of Pharmacology, Kyoto University Faculty of Medicine, Yoshida Konoe-cho, Sakyo-ku, Kyoto 606-8501, Japan
2 Laboratory of Membrane and Cytoskeleton Dynamics, Institute of Molecular and Cellular Biosciences, University of Tokyo, 1-1-1 Yayoi, Bunkyoku, Tokyo 113-0032, Japan
3 Precursory Research for Embryonic Science and Technology (PRESTO), Japan Science and Technology Agency (JST), Honcho, Kawaguchi-shi, Saitama 332-0012, Japan

* Author for correspondence (e-mail: naoki-w{at}mfour.med.kyoto-u.ac.jp)

Accepted 15 July 2008

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.

Key words: Formin, mDia, G-actin, Rho, Actin nucleation






© The Company of Biologists Ltd 2008