藤原 郁子 (フジワラ イクコ)

FUJIWARA Ikuko

写真a

所属学科・専攻等

リサーチ・アドミニストレーション・オフィス

職名

メールアドレス

メールアドレス

ホームページ

http://actinpolymerization.jimdo.com

研究分野・キーワード

生物物理学、細胞骨格、細胞運動のダイナミクス、力発生、タンパク質の熱力学

プロフィール

タンパク質の結合・解離がどのように相互作用しあって、集合体である細胞の運動機能を制御しているのかを調べています

出身大学

  •  
    -
    1998年03月

    早稲田大学   理工学部   応用物理学学科   卒業

出身大学院

  • 1998年04月
    -
    2003年03月

    早稲田大学大学院  理工学研究科  物理学及び応用物理学専攻博士課程  修了

学外略歴

  • 2014年04月
    -
    2014年12月

      京都大学 物質-細胞統合システム拠点 (iCeMS)   助教

  • 2006年09月
    -
    2014年03月

      米国立衛生研究所   National Heart, Lung and Blood Institute   研究員

  • 2004年08月
    -
    2006年09月

      エール大学   Molecular Cellular and Developmental Biology   研究員

所属学会・委員会

  • 1998年04月
    -
    継続中

    日本生物物理学会

  • 2018年04月
    -
    継続中

    日本細胞生物学会

  • 2010年10月
    -
    継続中

    米国細胞生物学会

専門分野(科研費分類)

  • 細胞生物学

  • 生物物理学

 

論文

  • Latrunculin A Accelerates Actin Filament Depolymerization in Addition to Sequestering Actin Monomers

    Fujiwara I, Zweifel ME, Courtemanche N, Pollard TD

    Current Biology ( Elsevier )    2018年09月  [査読有り]

    研究論文(学術雑誌)   共著

    Latrunculin A (LatA), a toxin from the red sea sponge Latrunculia magnifica, is the most widely used reagent to depolymerize actin filaments in experiments on live cells. LatA binds actin monomers and sequesters them from polymerization [1, 2]. Low concentrations of LatA result in rapid (tens of seconds) disassembly of actin filaments in animal [3] and yeast cells [2]. Depolymerization is usually assumed to result from sequestration of actin monomers. Our observations of single-muscle actin filaments by TIRF microscopy showed that LatA bound ATP-actin monomers with a higher affinity (Kd = 0.1 μM) than ADP-Pi-actin (Kd = 0.4 μM) or ADP-actin (Kd = 4.7 μM). LatA also slowly severed filaments and increased the depolymerization rate at both ends of filaments freshly assembled from ATP-actin to the rates of ADP-actin. This rate plateaued at LatA concentrations >60 μM. LatA did not change the depolymerization rates of ADP- actin filaments or ADP-Pi-actin filaments generated with 160 mM phosphate in the buffer. LatA did not increase the rate of phosphate release from bulk samples of filaments assembled from ATP-actin. Thermodynamic analysis showed that LatA binds weakly to actin filaments with a Kd >100 μM. We propose that concentrations of LatA much lower than this Kd promote phosphate dissociation only from both ends of filaments, resulting in depolymerization limited by the rate of ADP-actin dissociation. Thus, one must consider both rapid actin depolymerization and severing in addition to sequestering actin monomers when interpreting the effects of LatA on cells.

  • Keeping the focus on biophysics and actin filaments in Nagoya: A report of the 2016 "now in actin" symposium.

    Fujiwara, Ikuko and Narita, Akihiro

    Cytoskeleton ( Wiley )  74 ( 12 ) 450 - 464   2017年12月  [査読有り]  [招待有り]

    研究論文(学術雑誌)   共著

  • Capping protein regulatory cycle driven by CARMIL and V-1 may promote actin network assembly at protruding edges.

    Ikuko Fujiwara, Kirsten Remmert, Grzegorz Piszczek and John A. Hammer

    Proc Natl Acad Sci U S A.   111 ( 19 ) 1970 - 1977   2014年05月  [査読有り]

    研究論文(学術雑誌)   共著

    Assembly of actin filaments near the plasma membrane drives extension of the cell edge as it migrates. Cells recruit a protein machine called the Arp2/3 complex to the leading edge to initiate actin filament branches that grow and push on the membrane. Equally important, capping protein (CP) binds to and terminates polymerization of the fast-growing end of the filament. Like other aspects of actin assembly, CP is subject to regulation. Specifically, the protein V-1/myotrophin inactivates CP, while capping protein Arp2/3 myosin I linker (CARMIL) proteins moderately inhibit CP. We describe how CARMIL and V-1 cooperate in a cycle of reactions to regulate CP and promote assembly of the actin network by the Arp2/3 complex.

  • Morphology and viscoelasticity of actin networks formed with the mutually interacting crosslinkers: palladin and alpha-actinin.

    Grooman B, Fujiwara I, Otey C, Upadhyaya A.

    PLoS One   7 ( 8 ) e42773   2012年08月

    研究論文(学術雑誌)   共著

  • Structural basis for capping protein sequestration by myotrophin (V-1).

    Zwolak A, Fujiwara I, Hammer JA, Tjandra N.

    J Biol Chem.   285 ( 33 ) 25767 - 25781   2010年08月  [査読有り]

    研究論文(学術雑誌)   共著

    Capping protein (CP) is a ubiquitously expressed, heterodimeric 62-kDa protein that binds the barbed end of the actin filament with high affinity to block further filament elongation. Myotrophin (V-1) is a 13-kDa ankyrin repeat-containing protein that binds CP tightly, sequestering it in a totally inactive complex in vitro. Here, we elucidate the molecular interaction between CP and V-1 by NMR. Specifically, chemical shift mapping and intermolecular paramagnetic relaxation enhancement experiments reveal that the ankyrin loops of V-1, which are essential for V-1/CP interaction, bind the basic patch near the joint of the alpha tentacle of CP shown previously to drive most of the association of CP with and affinity for the barbed end. Consistently, site-directed mutagenesis of CP shows that V-1 and the strong electrostatic binding site for CP on the barbed end compete for this basic patch on CP. These results can explain how V-1 inactivates barbed end capping by CP and why V-1 is incapable of uncapping CP-capped actin filaments, the two signature biochemical activities of V-1.

  • Direct observation of the uncapping of capping protein-capped actin filaments by CARMIL homology domain 3.

    Fujiwara I, Remmert K, Hammer JA 3rd.

    J Biol Chem.   285 ( 4 ) 2707 - 2720   2010年06月

    研究論文(学術雑誌)   共著

  • Actin-bundling protein TRIOBP forms resilient rootlets of hair cell stereocilia essential for hearing.

    Kitajiri S, Sakamoto T, Belyantseva IA, Goodyear RJ, Stepanyan R, Fujiwara I, Bird JE, Riazuddin S, Riazuddin S, Ahmed ZM, Hinshaw JE, Sellers J, Bartles JR, Hammer JA 3rd, Richardson GP, Griffith AJ, Frolenkov GI, Friedman TB.

    Cell   141 ( 5 ) 786 - 798   2010年05月

    研究論文(学術雑誌)   共著

    Inner ear hair cells detect sound through deflection of mechanosensory stereocilia. Each stereocilium is supported by a paracrystalline array of parallel actin filaments that are packed more densely at the base, forming a rootlet extending into the cell body. The function of rootlets and the molecules responsible for their formation are unknown. We found that TRIOBP, a cytoskeleton-associated protein mutated in human hereditary deafness DFNB28, is localized to rootlets. In vitro, purified TRIOBP isoform 4 protein organizes actin filaments into uniquely dense bundles reminiscent of rootlets but distinct from bundles formed by espin, an actin crosslinker in stereocilia. We generated mutant Triobp mice (Triobp(Deltaex8/Deltaex8)) that are profoundly deaf. Stereocilia of Triobp(Deltaex8/Deltaex8) mice develop normally but fail to form rootlets and are easier to deflect and damage. Thus, F-actin bundling by TRIOBP provides durability and rigidity for normal mechanosensitivity of stereocilia and may contribute to resilient cytoskeletal structures elsewhere.

  • Automated actin filament segmentation, tracking and tip elongation measurements based on open active contour models

    Hongsheng Li ; Tian Shen ; Matthew B. Smith ; Ikuko Fujiwara ; Dimitrios Vavylonis ; Xiaolei Huang

    IEEE Xplore     1302 - 1305   2009年08月

    研究論文(学術雑誌)   共著

  • Human myosin Vc is a low duty ratio, nonprocessive molecular motor.

    Takagi Y, Yang Y, Fujiwara I, Jacobs D, Cheney RE, Sellers JR, Kovács M.

    J Biol Chem.   283 ( 13 ) 8527 - 8537   2008年05月

    研究論文(学術雑誌)   共著

  • Leiomodin is an actin filament nucleator in muscle cells

    Chereau D, Boczkowska M, Skwarek-Maruszewska A, Fujiwara I, Hayes DB, Rebowski G, Lappalainen P, Pollard TD, Dominguez R.

    Science ( AAAS )  320 ( 5873 ) 239 - 243   2008年04月  [査読有り]

    研究論文(学術雑誌)   共著

    Initiation of actin polymerization in cells requires nucleation factors. Here we describe an actin-binding protein, leiomodin, that acted as a strong filament nucleator in muscle cells. Leiomodin shared two actin-binding sites with the filament pointed end-capping protein tropomodulin: a flexible N-terminal region and a leucine-rich repeat domain. Leiomodin also contained a C-terminal extension of 150 residues. The smallest fragment with strong nucleation activity included the leucine-rich repeat and C-terminal extension. The N-terminal region enhanced the nucleation activity threefold and recruited tropomyosin, which weakly stimulated nucleation and mediated localization of leiomodin to the middle of muscle sarcomeres. Knocking down leiomodin severely compromised sarcomere assembly in cultured muscle cells, which suggests a role for leiomodin in the nucleation of tropomyosin-decorated filaments in muscles.

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著書

  • 一分子生物学

    藤原郁子 (石渡信一, 原田慶恵 編) (担当: 分担執筆 )

    同仁化学出版  2014年06月

研究発表

  • LOVを導入したファシンによるアクチン束化の制御

    Ikuko Fujiwara, Miki Iwatani, Yumeka Yamauchi, Tatsuya Iwata, Shuichi Takeda, Toshiro Oda, Tomoharu Matsumoto, Akihiro Narita, Satoshi Tsunoda, Hideki Kandori

    第56回日本生物物理学会年会  (岡山大学)  2018年09月  -  2018年09月  日本生物物理学会

  • Single actin filaments observation revealed that Latrunculin A depolymerizes actin filaments in addition to sequestering actin monomers

    Ikuko Fujiwara, Mark E. Zweifel, Naomi Courtemanche, Thomas D. Pollard

    日本細胞生物学会  (タワーホール船堀、東京)  2018年06月  -  2018年06月  日本細胞生物学会(日本発生生物学会合同大会)

  • タンパク質の創発する集合知

    藤原郁子  [招待有り]

    第3回 市民共創研究会  (名古屋工業大学)  2017年12月  -  2017年12月  人工知能学会 市民共創知研究会

  • Regulation of actin bundles by using LOV-fused fascin

    藤原郁子, 岩谷三樹, 岩田達也, 角田聡, 神取秀樹

    Optogentics Research Society   (仙台)  2017年10月  -  2017年10月 

  • Severing regulation of gelsolin superfamily on single and bundled actin filaments.

    Ikuko Fujiwara, Rachel Fan, Shuichi Takeda, Yuichiro Maéda and Akihiro Narita

    International Symposium, Harmonized supramolecular motility machinery and its diversity  (名古屋大学)  2017年09月  -  2017年09月 

  • A CARMIL and V-1/Myotrophin -Dependent Regulatory Cycle for Capping Protein May Potentiate Actin Polymerization at the Plasma Membrane: Cytosol Interface

    Fujiwara, I., Remmert, K., Piszczek, G., Hammer, JA.

    ASCB (American Society of Cell Biology)  2012年12月  -  2012年12月 

  • Myosin 18A-alpha is highly concentrated in the dendritic spines of mouse cerebellar Purkinje neurons: possible implications for spine morphogenesis and function

    Barzik, M., Fujiwara, I., Petralia, RS, Yang, Y., Sellers, JR., Hammer, JA

    ASCB (American Society of Cell Biology)  (San Francisco)  2012年12月  -  2012年12月 

  • アクチンのフィラメント化とモノマー化:細胞が動き続けるメカニズムの原型

    藤原郁子、Kirsten Remmert、John A. Hammer III  [招待有り]

    日本農芸化学会関東支部会第二回例会  (つくば)  2012年01月  -  2012年01月  日本農芸化学会

  • Total internal reflection fluorescence microscopic determination of polymerization kinetics of ADP and ADP-Pi actin

    Fujiwara, I., Kuhn, J., Mahaffy, R., Pollard, TD.

    Biophysical Soeicty  (Uta, USA)  2006年02月  -  2006年02月  Biophysical Soeicty

  • Microscopic analysis of polymerization and depolymerization dynamics of single actin filaments-Effects of regulatory proteins and Pi

    Fujiwara, I., Sasaki, D., Ishiwata, S

    Biophysical Soeicty  2003年02月  -  2003年02月  Biophysical Soeicty

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学術関係受賞

  • recommended in F1000Prime as being of special significance in its field by F1000

    2018年10月16日   Faculty of 1000 Ltd | Science Navigation Group   Latrunculin A accelerates actin filament depolymerization in addition to sequestering actin monomers  

    受賞者:  Fujiwara I, Zweifel ME, Courtemanche N, Pollard TD

    A continually updated collection of over 145,000 recommendations of top articles in biology and medicine, contributed by the F1000 Faculty.

科研費(文科省・学振)獲得実績

  • ゲルゾリン様タンパク質によるアクチン繊維切断機構の解明

    基盤研究(C)

    研究期間:  2017年04月  -  2020年03月  代表者:  小田 俊郎

  • 細胞伸張制御におけるアクチン重合調節タンパク質CPの役割

    若手研究(B)

    研究期間:  2015年04月  -  2017年03月  代表者:  藤原郁子

 

その他教育活動及び特記事項

  • 2016年07月
     
     

    外国人研究者のための科研費申請書の書き方講習 Euraxess(EU在日研究者支援団体)主催

 

学会・委員会等活動

  • 2018年01月
    -
    現在

    日本生物物理学会   名古屋工業大学ダイバーシティ推進センター スーパーバイザー

  • 2016年11月
    -
    現在

    日本生物物理学会   American Society For Cell Biology (ASCB) 名古屋工業大学 アンバサダー

社会貢献活動

  • 「生物物理学を語る――研究最前線の若い女性研究者たち」

    美宅成樹 (生物物理学会会長)  (横浜)  2007年12月  -  2007年12月