Note to users. If you're seeing this message, it means that your browser cannot find this page's style/presentation instructions -- or possibly that you are using a browser that does not support current Web standards. Find out more about why this message is appearing, and what you can do to make your experience of our site the best it can be.


Logo for

Science 303 (5666): 2007-2010

Copyright © 2004 by the American Association for the Advancement of Science

Actin Polymerization-Driven Molecular Movement of mDia1 in Living Cells

Chiharu Higashida,1 Takushi Miyoshi,1 Akiko Fujita,1 Fabian Oceguera-Yanez,1 James Monypenny,1 Yoshikazu Andou,1 Shuh Narumiya,1 Naoki Watanabe1,2*

Abstract: mDia1, a Rho effector, belongs to the Formin family of proteins, which shares the conserved tandem FH1-FH2 unit structure. Formins including mDia1 accelerate actin nucleation while interacting with actin filament fast-growing ends. Here our single-molecule imaging revealed fast directional movement of mDia1 FH1-FH2 for tens of microns in living cells. The movement of mDia1 FH1-FH2 was blocked by actin-perturbing drugs, and the speed of mDia1 FH1-FH2 movement appeared to correlate with actin elongation rates. In vitro, mDia1 FH1-FH2 associated persistently with the growing actin barbed end. mDia1 probably moves processively along the growing end of actin filaments in cells, and Formins may be a molecular motility machinery that is independent from motor proteins.

1 Department of Pharmacology, Kyoto University Faculty of Medicine, Yoshida Konoe-cho, Sakyo-ku, Kyoto, Japan.
2 PRESTO, Japan Science and Technology Agency, 4-1-8 Honcho Kawaguchi, Saitama, Japan.

* To whom correspondence should be addressed. E-mail: naoki-w{at}

FHOD1 regulates stress fiber organization by controlling the dynamics of transverse arcs and dorsal fibers.
N. Schulze, M. Graessl, A. Blancke Soares, M. Geyer, L. Dehmelt, and P. Nalbant (2014)
J. Cell Sci. 127, 1379-1393
   Abstract »    Full Text »    PDF »
New single-molecule speckle microscopy reveals modification of the retrograde actin flow by focal adhesions at nanometer scales.
S. Yamashiro, H. Mizuno, M. B. Smith, G. L. Ryan, T. Kiuchi, D. Vavylonis, and N. Watanabe (2014)
Mol. Biol. Cell 25, 1010-1024
   Abstract »    Full Text »    PDF »
Actin Dynamics, Architecture, and Mechanics in Cell Motility.
L. Blanchoin, R. Boujemaa-Paterski, C. Sykes, and J. Plastino (2014)
Physiol Rev 94, 235-263
   Abstract »    Full Text »    PDF »
Citron kinase mediates transition from constriction to abscission through its coiled-coil domain.
S. Watanabe, T. De Zan, T. Ishizaki, and S. Narumiya (2013)
J. Cell Sci. 126, 1773-1784
   Abstract »    Full Text »    PDF »
FHOD1 is a combined actin filament capping and bundling factor that selectively associates with actin arcs and stress fibers.
A. Schonichen, H. G. Mannherz, E. Behrmann, A. J. Mazur, S. Kuhn, U. Silvan, C.-A. Schoenenberger, O. T. Fackler, S. Raunser, L. Dehmelt, et al. (2013)
J. Cell Sci. 126, 1891-1901
   Abstract »    Full Text »    PDF »
Actin-capping protein promotes microtubule stability by antagonizing the actin activity of mDia1.
F. Bartolini, N. Ramalingam, and G. G. Gundersen (2012)
Mol. Biol. Cell 23, 4032-4040
   Abstract »    Full Text »    PDF »
Autoinhibition of the formin Cappuccino in the absence of canonical autoinhibitory domains.
B. Bor, C. L. Vizcarra, M. L. Phillips, and M. E. Quinlan (2012)
Mol. Biol. Cell 23, 3801-3813
   Abstract »    Full Text »    PDF »
Caveolar domain organization and trafficking is regulated by Abl kinases and mDia1.
A. Echarri, O. Muriel, D. M. Pavon, H. Azegrouz, F. Escolar, M. C. Terron, F. Sanchez-Cabo, F. Martinez, M. C. Montoya, O. Llorca, et al. (2012)
J. Cell Sci. 125, 3097-3113
   Abstract »    Full Text »    PDF »
The Arp2/3 complex is required for lamellipodia extension and directional fibroblast cell migration.
P. Suraneni, B. Rubinstein, J. R. Unruh, M. Durnin, D. Hanein, and R. Li (2012)
J. Cell Biol. 197, 239-251
   Abstract »    Full Text »    PDF »
Signal Transduction in Receptor for Advanced Glycation End Products (RAGE): SOLUTION STRUCTURE OF C-TERMINAL RAGE (ctRAGE) AND ITS BINDING TO mDia1.
V. Rai, A. Y. Maldonado, D. S. Burz, S. Reverdatto, A. M. Schmidt, and A. Shekhtman (2012)
J. Biol. Chem. 287, 5133-5144
   Abstract »    Full Text »    PDF »
Liprin-{alpha} controls stress fiber formation by binding to mDia and regulating its membrane localization.
S. Sakamoto, T. Ishizaki, K. Okawa, S. Watanabe, T. Arakawa, N. Watanabe, and S. Narumiya (2012)
J. Cell Sci. 125, 108-120
   Abstract »    Full Text »    PDF »
Involvement of the Rho-mDia1 pathway in the regulation of Golgi complex architecture and dynamics.
Y. Zilberman, N. O. Alieva, S. Miserey-Lenkei, A. Lichtenstein, Z. Kam, H. Sabanay, and A. Bershadsky (2011)
Mol. Biol. Cell 22, 2900-2911
   Abstract »    Full Text »    PDF »
Cortical actin dynamics driven by formins and myosin V.
J. H. Yu, A. H. Crevenna, M. Bettenbuhl, T. Freisinger, and R. Wedlich-Soldner (2011)
J. Cell Sci. 124, 1533-1541
   Abstract »    Full Text »    PDF »
Rotational Movement of the Formin mDia1 Along the Double Helical Strand of an Actin Filament.
H. Mizuno, C. Higashida, Y. Yuan, T. Ishizaki, S. Narumiya, and N. Watanabe (2011)
Science 331, 80-83
   Abstract »    Full Text »    PDF »
mDia1 Targets v-Src to the Cell Periphery and Facilitates Cell Transformation, Tumorigenesis, and Invasion.
M. Tanji, T. Ishizaki, S. Ebrahimi, Y. Tsuboguchi, T. Sukezane, T. Akagi, M. C. Frame, N. Hashimoto, S. Miyamoto, and S. Narumiya (2010)
Mol. Cell. Biol. 30, 4604-4615
   Abstract »    Full Text »    PDF »
Characterization of the Biochemical Properties and Biological Function of the Formin Homology Domains of Drosophila DAAM.
S. Barko, B. Bugyi, M.-F. Carlier, R. Gombos, T. Matusek, J. Mihaly, and M. Nyitrai (2010)
J. Biol. Chem. 285, 13154-13169
   Abstract »    Full Text »    PDF »
Requirement for Formin-Induced Actin Polymerization during Spread of Shigella flexneri.
J. E. Heindl, I. Saran, C.-r. Yi, C. F. Lesser, and M. B. Goldberg (2010)
Infect. Immun. 78, 193-203
   Abstract »    Full Text »    PDF »
Arabidopsis Formin3 Directs the Formation of Actin Cables and Polarized Growth in Pollen Tubes.
J. Ye, Y. Zheng, A. Yan, N. Chen, Z. Wang, S. Huang, and Z. Yang (2009)
PLANT CELL 21, 3868-3884
   Abstract »    Full Text »    PDF »
Myosin II regulation during C. elegans embryonic elongation: LET-502/ROCK, MRCK-1 and PAK-1, three kinases with different roles.
C. Gally, F. Wissler, H. Zahreddine, S. Quintin, F. Landmann, and M. Labouesse (2009)
Development 136, 3109-3119
   Abstract »    Full Text »    PDF »
Energetic Requirements for Processive Elongation of Actin Filaments by FH1FH2-formins.
A. S. Paul and T. D. Pollard (2009)
J. Biol. Chem. 284, 12533-12540
   Abstract »    Full Text »    PDF »
Diaphanous-Related Formins Are Required for Invadopodia Formation and Invasion of Breast Tumor Cells.
F. Lizarraga, R. Poincloux, M. Romao, G. Montagnac, G. Le Dez, I. Bonne, G. Rigaill, G. Raposo, and P. Chavrier (2009)
Cancer Res. 69, 2792-2800
   Abstract »    Full Text »    PDF »
Imatinib Mesylate (STI571)-Induced Cell Edge Translocation of Kinase-Active and Kinase-Defective Abelson Kinase: Requirements of Myristoylation and src Homology 3 Domain.
A. Fujita, T. Shishido, Y. Yuan, E. Inamoto, S. Narumiya, and N. Watanabe (2009)
Mol. Pharmacol. 75, 75-84
   Abstract »    Full Text »    PDF »
Specificity of Interactions between mDia Isoforms and Rho Proteins.
M. Lammers, S. Meyer, D. Kuhlmann, and A. Wittinghofer (2008)
J. Biol. Chem. 283, 35236-35246
   Abstract »    Full Text »    PDF »
Shootin1 interacts with actin retrograde flow and L1-CAM to promote axon outgrowth.
T. Shimada, M. Toriyama, K. Uemura, H. Kamiguchi, T. Sugiura, N. Watanabe, and N. Inagaki (2008)
J. Cell Biol. 181, 817-829
   Abstract »    Full Text »    PDF »
G-actin regulates rapid induction of actin nucleation by mDia1 to restore cellular actin polymers.
C. Higashida, S. Suetsugu, T. Tsuji, J. Monypenny, S. Narumiya, and N. Watanabe (2008)
J. Cell Sci. 121, 3403-3412
   Abstract »    Full Text »    PDF »
The formin mDia2 stabilizes microtubules independently of its actin nucleation activity.
F. Bartolini, J. B. Moseley, J. Schmoranzer, L. Cassimeris, B. L. Goode, and G. G. Gundersen (2008)
J. Cell Biol. 181, 523-536
   Abstract »    Full Text »    PDF »
Actin disassembly by cofilin, coronin, and Aip1 occurs in bursts and is inhibited by barbed-end cappers.
H. Y. Kueh, G. T. Charras, T. J. Mitchison, and W. M. Brieher (2008)
J. Cell Biol. 182, 341-353
   Abstract »    Full Text »    PDF »
Regulation and Targeting of the Fission Yeast Formin cdc12p in Cytokinesis.
A. Yonetani, R. J. Lustig, J. B. Moseley, T. Takeda, B. L. Goode, and F. Chang (2008)
Mol. Biol. Cell 19, 2208-2219
   Abstract »    Full Text »    PDF »
mDia2 regulates actin and focal adhesion dynamics and organization in the lamella for efficient epithelial cell migration.
S. L. Gupton, K. Eisenmann, A. S. Alberts, and C. M. Waterman-Storer (2007)
J. Cell Sci. 120, 3475-3487
   Abstract »    Full Text »    PDF »
Impaired T lymphocyte trafficking in mice deficient in an actin-nucleating protein, mDia1.
D. Sakata, H. Taniguchi, S. Yasuda, A. Adachi-Morishima, Y. Hamazaki, R. Nakayama, T. Miki, N. Minato, and S. Narumiya (2007)
J. Exp. Med. 204, 2031-2038
   Abstract »    Full Text »    PDF »
Yeast Formins Bni1 and Bnr1 Utilize Different Modes of Cortical Interaction during the Assembly of Actin Cables.
S. M. Buttery, S. Yoshida, and D. Pellman (2007)
Mol. Biol. Cell 18, 1826-1838
   Abstract »    Full Text »    PDF »
How ATP Hydrolysis Controls Filament Assembly from Profilin-Actin: IMPLICATION FOR FORMIN PROCESSIVITY.
S. Romero, D. Didry, E. Larquet, N. Boisset, D. Pantaloni, and M.-F. Carlier (2007)
J. Biol. Chem. 282, 8435-8445
   Abstract »    Full Text »    PDF »
RhoA-Dependent Vascular Smooth Muscle Cell-Specific Transcription: Adding Diaphanous Formins to the Puzzle.
E. Larsson, X. Zhou, and L. M. Akyurek (2007)
Arterioscler Thromb Vasc Biol 27, 448-449
   Full Text »    PDF »
Agrin and laminin induce acetylcholine receptor clustering by convergent, Rho GTPase-dependent signaling pathways.
C. A. Weston, G. Teressa, B. S. Weeks, and J. Prives (2007)
J. Cell Sci. 120, 868-875
   Abstract »    Full Text »    PDF »
Diaphanous 1 and 2 Regulate Smooth Muscle Cell Differentiation by Activating the Myocardin-Related Transcription Factors.
D. P. Staus, A. L. Blaker, J. M. Taylor, and C. P. Mack (2007)
Arterioscler Thromb Vasc Biol 27, 478-486
   Abstract »    Full Text »    PDF »
Actin turnover-dependent fast dissociation of capping protein in the dendritic nucleation actin network: evidence of frequent filament severing.
T. Miyoshi, T. Tsuji, C. Higashida, M. Hertzog, A. Fujita, S. Narumiya, G. Scita, and N. Watanabe (2006)
J. Cell Biol. 175, 947-955
   Abstract »    Full Text »    PDF »
Reassembly of contractile actin cortex in cell blebs.
G. T. Charras, C.-K. Hu, M. Coughlin, and T. J. Mitchison (2006)
J. Cell Biol. 175, 477-490
   Abstract »    Full Text »    PDF »
Rapid actin monomer-insensitive depolymerization of Listeria actin comet tails by cofilin, coronin, and Aip1.
W. M. Brieher, H. Y. Kueh, B. A. Ballif, and T. J. Mitchison (2006)
J. Cell Biol. 175, 315-324
   Abstract »    Full Text »    PDF »
The Rho-mDia1 Pathway Regulates Cell Polarity and Focal Adhesion Turnover in Migrating Cells through Mobilizing Apc and c-Src.
N. Yamana, Y. Arakawa, T. Nishino, K. Kurokawa, M. Tanji, R. E. Itoh, J. Monypenny, T. Ishizaki, H. Bito, K. Nozaki, et al. (2006)
Mol. Cell. Biol. 26, 6844-6858
   Abstract »    Full Text »    PDF »
The Yeast Actin Cytoskeleton: from Cellular Function to Biochemical Mechanism.
J. B. Moseley and B. L. Goode (2006)
Microbiol. Mol. Biol. Rev. 70, 605-645
   Abstract »    Full Text »    PDF »
The bundling activity of vasodilator-stimulated phosphoprotein is required for filopodium formation.
A. Schirenbeck, R. Arasada, T. Bretschneider, T. E. B. Stradal, M. Schleicher, and J. Faix (2006)
PNAS 103, 7694-7699
   Abstract »    Full Text »    PDF »
Stress fibers are generated by two distinct actin assembly mechanisms in motile cells.
P. Hotulainen and P. Lappalainen (2006)
J. Cell Biol. 173, 383-394
   Abstract »    Full Text »    PDF »
Mammalian twinfilin sequesters ADP-G-actin and caps filament barbed ends: implications in motility.
E. Helfer, E. M. Nevalainen, P. Naumanen, S. Romero, D. Didry, D. Pantaloni, P. Lappalainen, and M.-F. Carlier (2006)
EMBO J. 25, 1184-1195
   Abstract »    Full Text »    PDF »
Biochemical Characterization of the Diaphanous Autoregulatory Interaction in the Formin Homology Protein FHOD1.
A. Schonichen, M. Alexander, J. E. Gasteier, F. E. Cuesta, O. T. Fackler, and M. Geyer (2006)
J. Biol. Chem. 281, 5084-5093
   Abstract »    Full Text »    PDF »
The regulation of mDia1 by autoinhibition and its release by Rho*GTP.
M. Lammers, R. Rose, A. Scrima, and A. Wittinghofer (2005)
EMBO J. 24, 4176-4187
   Abstract »    Full Text »    PDF »
A novel mechanism of actin filament processive capping by formin: solution of the rotation paradox.
T. Shemesh, T. Otomo, M. K. Rosen, A. D. Bershadsky, and M. M. Kozlov (2005)
J. Cell Biol. 170, 889-893
   Abstract »    Full Text »    PDF »
The Formin Homology 1 Domain Modulates the Actin Nucleation and Bundling Activity of Arabidopsis FORMIN1.
A. Michelot, C. Guerin, S. Huang, M. Ingouff, S. Richard, N. Rodiuc, C. J. Staiger, and L. Blanchoin (2005)
PLANT CELL 17, 2296-2313
   Abstract »    Full Text »    PDF »
Subsecond reorganization of the actin network in cell motility and chemotaxis.
S. Diez, G. Gerisch, K. Anderson, A. Muller-Taubenberger, and T. Bretschneider (2005)
PNAS 102, 7601-7606
   Abstract »    Full Text »    PDF »
Profilin-mediated Competition between Capping Protein and Formin Cdc12p during Cytokinesis in Fission Yeast.
D. R. Kovar, J.-Q. Wu, and T. D. Pollard (2005)
Mol. Biol. Cell 16, 2313-2324
   Abstract »    Full Text »    PDF »
RhoGEF2 and the formin Dia control the formation of the furrow canal by directed actin assembly during Drosophila cellularisation.
J. Grosshans, C. Wenzl, H.-M. Herz, S. Bartoszewski, F. Schnorrer, N. Vogt, H. Schwarz, and H.-A. Muller (2005)
Development 132, 1009-1020
   Abstract »    Full Text »    PDF »
Dissecting Requirements for Auto-inhibition of Actin Nucleation by the Formin, mDia1.
F. Li and H. N. Higgs (2005)
J. Biol. Chem. 280, 6986-6992
   Abstract »    Full Text »    PDF »
The role of the Rho GTPases in neuronal development.
E.-E. Govek, S. E. Newey, and L. Van Aelst (2005)
Genes & Dev. 19, 1-49
   Abstract »    Full Text »    PDF »
Processive capping by formin suggests a force-driven mechanism of actin polymerization.
M. M. Kozlov and A. D. Bershadsky (2004)
J. Cell Biol. 167, 1011-1017
   Abstract »    Full Text »    PDF »
Insertional assembly of actin filament barbed ends in association with formins produces piconewton forces.
D. R. Kovar and T. D. Pollard (2004)
PNAS 101, 14725-14730
   Abstract »    Full Text »    PDF »
Two Distinct Actin Networks Drive the Protrusion of Migrating Cells.
A. Ponti, M. Machacek, S. L. Gupton, C. M. Waterman-Storer, and G. Danuser (2004)
Science 305, 1782-1786
   Abstract »    Full Text »    PDF »
Activation of Endogenous Cdc42 Visualized in Living Cells.
P. Nalbant, L. Hodgson, V. Kraynov, A. Toutchkine, and K. M. Hahn (2004)
Science 305, 1615-1619
   Abstract »    Full Text »    PDF »

To Advertise     Find Products

Science Signaling. ISSN 1937-9145 (online), 1945-0877 (print). Pre-2008: Science's STKE. ISSN 1525-8882