Biphasic Effect of Profilin Impacts the Formin mDia1 Force-Sensing Mechanism in Actin Polymerization

Hiroaki Kubota, Makito Miyazaki, Taisaku Ogawa, Togo Shimozawa, Kazuhiko Kinosita, Shin'ichi Ishiwata

    Research output: Contribution to journalArticle

    18 Citations (Scopus)

    Abstract

    Formins are force-sensing proteins that regulate actin polymerization dynamics. Here, we applied stretching tension to individual actin filaments under the regulation of formin mDia1 to investigate the mechanical responses in actin polymerization dynamics. We found that the elongation of an actin filament was accelerated to a greater degree by stretching tension for ADP-G-actin than that for ATP-G-actin. An apparent decrease in the critical concentration of G-actin was observed, especially in ADP-G-actin. These results on two types of G-actin were reproduced by a simple kinetic model, assuming the rapid equilibrium between pre- and posttranslocated states of the formin homology domain two dimer. In addition, profilin concentration dramatically altered the force-dependent acceleration of actin filament elongation, which ranged from twofold to an all-or-none response. Even under conditions in which actin depolymerization occurred, applications of a several-piconewton stretching tension triggered rapid actin filament elongation. This extremely high force-sensing mechanism of mDia1 and profilin could be explained by the force-dependent coordination of the biphasic effect of profilin; i.e., an acceleration effect masked by a depolymerization effect became dominant under stretching tension, negating the latter to rapidly enhance the elongation rate. Our findings demonstrate that the biphasic effect of profilin is controlled by mechanical force, thus expanding the function of mDia1 as a mechanosensitive regulator of actin polymerization.

    Original languageEnglish
    Pages (from-to)461-471
    Number of pages11
    JournalBiophysical Journal
    Volume113
    Issue number2
    DOIs
    Publication statusPublished - 2017 Jul 25

    Fingerprint

    Profilins
    Polymerization
    Actins
    Actin Cytoskeleton

    ASJC Scopus subject areas

    • Biophysics

    Cite this

    Kubota, H., Miyazaki, M., Ogawa, T., Shimozawa, T., Kinosita, K., & Ishiwata, S. (2017). Biphasic Effect of Profilin Impacts the Formin mDia1 Force-Sensing Mechanism in Actin Polymerization. Biophysical Journal, 113(2), 461-471. https://doi.org/10.1016/j.bpj.2017.06.012

    Biphasic Effect of Profilin Impacts the Formin mDia1 Force-Sensing Mechanism in Actin Polymerization. / Kubota, Hiroaki; Miyazaki, Makito; Ogawa, Taisaku; Shimozawa, Togo; Kinosita, Kazuhiko; Ishiwata, Shin'ichi.

    In: Biophysical Journal, Vol. 113, No. 2, 25.07.2017, p. 461-471.

    Research output: Contribution to journalArticle

    Kubota, H, Miyazaki, M, Ogawa, T, Shimozawa, T, Kinosita, K & Ishiwata, S 2017, 'Biphasic Effect of Profilin Impacts the Formin mDia1 Force-Sensing Mechanism in Actin Polymerization', Biophysical Journal, vol. 113, no. 2, pp. 461-471. https://doi.org/10.1016/j.bpj.2017.06.012
    Kubota, Hiroaki ; Miyazaki, Makito ; Ogawa, Taisaku ; Shimozawa, Togo ; Kinosita, Kazuhiko ; Ishiwata, Shin'ichi. / Biphasic Effect of Profilin Impacts the Formin mDia1 Force-Sensing Mechanism in Actin Polymerization. In: Biophysical Journal. 2017 ; Vol. 113, No. 2. pp. 461-471.
    @article{d741abaff26a439ea20dbbc51b402651,
    title = "Biphasic Effect of Profilin Impacts the Formin mDia1 Force-Sensing Mechanism in Actin Polymerization",
    abstract = "Formins are force-sensing proteins that regulate actin polymerization dynamics. Here, we applied stretching tension to individual actin filaments under the regulation of formin mDia1 to investigate the mechanical responses in actin polymerization dynamics. We found that the elongation of an actin filament was accelerated to a greater degree by stretching tension for ADP-G-actin than that for ATP-G-actin. An apparent decrease in the critical concentration of G-actin was observed, especially in ADP-G-actin. These results on two types of G-actin were reproduced by a simple kinetic model, assuming the rapid equilibrium between pre- and posttranslocated states of the formin homology domain two dimer. In addition, profilin concentration dramatically altered the force-dependent acceleration of actin filament elongation, which ranged from twofold to an all-or-none response. Even under conditions in which actin depolymerization occurred, applications of a several-piconewton stretching tension triggered rapid actin filament elongation. This extremely high force-sensing mechanism of mDia1 and profilin could be explained by the force-dependent coordination of the biphasic effect of profilin; i.e., an acceleration effect masked by a depolymerization effect became dominant under stretching tension, negating the latter to rapidly enhance the elongation rate. Our findings demonstrate that the biphasic effect of profilin is controlled by mechanical force, thus expanding the function of mDia1 as a mechanosensitive regulator of actin polymerization.",
    author = "Hiroaki Kubota and Makito Miyazaki and Taisaku Ogawa and Togo Shimozawa and Kazuhiko Kinosita and Shin'ichi Ishiwata",
    year = "2017",
    month = "7",
    day = "25",
    doi = "10.1016/j.bpj.2017.06.012",
    language = "English",
    volume = "113",
    pages = "461--471",
    journal = "Biophysical Journal",
    issn = "0006-3495",
    publisher = "Biophysical Society",
    number = "2",

    }

    TY - JOUR

    T1 - Biphasic Effect of Profilin Impacts the Formin mDia1 Force-Sensing Mechanism in Actin Polymerization

    AU - Kubota, Hiroaki

    AU - Miyazaki, Makito

    AU - Ogawa, Taisaku

    AU - Shimozawa, Togo

    AU - Kinosita, Kazuhiko

    AU - Ishiwata, Shin'ichi

    PY - 2017/7/25

    Y1 - 2017/7/25

    N2 - Formins are force-sensing proteins that regulate actin polymerization dynamics. Here, we applied stretching tension to individual actin filaments under the regulation of formin mDia1 to investigate the mechanical responses in actin polymerization dynamics. We found that the elongation of an actin filament was accelerated to a greater degree by stretching tension for ADP-G-actin than that for ATP-G-actin. An apparent decrease in the critical concentration of G-actin was observed, especially in ADP-G-actin. These results on two types of G-actin were reproduced by a simple kinetic model, assuming the rapid equilibrium between pre- and posttranslocated states of the formin homology domain two dimer. In addition, profilin concentration dramatically altered the force-dependent acceleration of actin filament elongation, which ranged from twofold to an all-or-none response. Even under conditions in which actin depolymerization occurred, applications of a several-piconewton stretching tension triggered rapid actin filament elongation. This extremely high force-sensing mechanism of mDia1 and profilin could be explained by the force-dependent coordination of the biphasic effect of profilin; i.e., an acceleration effect masked by a depolymerization effect became dominant under stretching tension, negating the latter to rapidly enhance the elongation rate. Our findings demonstrate that the biphasic effect of profilin is controlled by mechanical force, thus expanding the function of mDia1 as a mechanosensitive regulator of actin polymerization.

    AB - Formins are force-sensing proteins that regulate actin polymerization dynamics. Here, we applied stretching tension to individual actin filaments under the regulation of formin mDia1 to investigate the mechanical responses in actin polymerization dynamics. We found that the elongation of an actin filament was accelerated to a greater degree by stretching tension for ADP-G-actin than that for ATP-G-actin. An apparent decrease in the critical concentration of G-actin was observed, especially in ADP-G-actin. These results on two types of G-actin were reproduced by a simple kinetic model, assuming the rapid equilibrium between pre- and posttranslocated states of the formin homology domain two dimer. In addition, profilin concentration dramatically altered the force-dependent acceleration of actin filament elongation, which ranged from twofold to an all-or-none response. Even under conditions in which actin depolymerization occurred, applications of a several-piconewton stretching tension triggered rapid actin filament elongation. This extremely high force-sensing mechanism of mDia1 and profilin could be explained by the force-dependent coordination of the biphasic effect of profilin; i.e., an acceleration effect masked by a depolymerization effect became dominant under stretching tension, negating the latter to rapidly enhance the elongation rate. Our findings demonstrate that the biphasic effect of profilin is controlled by mechanical force, thus expanding the function of mDia1 as a mechanosensitive regulator of actin polymerization.

    UR - http://www.scopus.com/inward/record.url?scp=85025672113&partnerID=8YFLogxK

    UR - http://www.scopus.com/inward/citedby.url?scp=85025672113&partnerID=8YFLogxK

    U2 - 10.1016/j.bpj.2017.06.012

    DO - 10.1016/j.bpj.2017.06.012

    M3 - Article

    C2 - 28746856

    AN - SCOPUS:85025672113

    VL - 113

    SP - 461

    EP - 471

    JO - Biophysical Journal

    JF - Biophysical Journal

    SN - 0006-3495

    IS - 2

    ER -