Roles of cofilin regulation for polarity formation during cell migration and division

• Project/Area Number: 19370079
• Research Category: Grant-in-Aid for Scientific Research (B)
• Allocation Type: Single-year Grants
• Section: 一般
• Research Field: Cell biology
• Research Institution: Tohoku University
• Principal Investigator: MIZUNO Kensaku Tohoku University, 大学院・生命科学研究科, 教授 (70128396)
• Project Period (FY): 2007 – 2008
• Project Status: Completed (Fiscal Year 2008)
• Budget Amount: ¥18,460,000 (Direct Cost: ¥14,200,000、Indirect Cost: ¥4,260,000); Fiscal Year 2008: ¥8,580,000 (Direct Cost: ¥6,600,000、Indirect Cost: ¥1,980,000); Fiscal Year 2007: ¥9,880,000 (Direct Cost: ¥7,600,000、Indirect Cost: ¥2,280,000)
• Keywords: アクチン細胞骨格 / シグナル伝達 / LIMキナーゼ / コフィリン / Slingshot / 細胞極性 / 細胞運動 / 細胞分裂

Research Abstract

アクチン脱重合因子であるコフィリンは、アクチン骨格の再構築において中心的な役割を果たしており、リン酸化により活性が制御される。本研究では、生細胞内でのアクチン単量体の時空間的変化の測定系を開発し、細胞遊走時の仮足形成におけるコフィリンの重要性を解明した。また、細胞遊走時の極性形成、細胞分裂時の分裂軸決定、癌細胞浸潤、神経突起形成におけるコフィリンのリン酸化制御機構の重要性を明らかにした。

Research Products

• [Journal Article] Protein kinase D1 regulates cofilin-mediated F-actin reorganization and cell motility via Slingshot (2009)
  • Author(s): Eiseler, T., Doppler, H., Yan, I. K., Kitatani, K., Mizuno, K., and Storz, P.
  • Journal Title: Nat.Cell Biol. 11 Pages: 545-556
• [Journal Article] MST2-and Furry-mediated activation of NDR1 is critical for precise alignment of mitotic chromosomes (2009)
  • Author(s): Chiba, S., Ikeda, M., Katsunuma, K., Ohashi, K.,and Mizuno, K.
  • Journal Title: Curr.Biol. 19 Pages: 675-681
• [Journal Article] MST2- and Furry-mediated activation of NDR1 is critical for precise alignment of mitotic chromosomes (2009)
  • Author(s): Chiba, S., et.al.
  • Journal Title: Curr. Biol. (印刷中)
  • Peer Reviewed
• [Journal Article] Protein kinase D1 regulates cofilin activity, F-actin reorganization and cell motility via Slingshot (2009)
  • Author(s): Eiseler, T., et.al.
  • Journal Title: Nat. Cell Biol. (印刷中)
  • Peer Reviewed
• [Journal Article] Molecular dissection of the mechanisms of substrate recognition and F-actin-mediated activation of cofilin-phosphatase Slingshot-1 (2008)
  • Author(s): Kurita, S., Watanabe, Y., Gunji, E., Ohashi, K.,and Mizuno, K.
  • Journal Title: J.Biol.Chem. 283 Pages: 32542-32552
• [Journal Article] Critical roles of actin-interacting protein 1 in cytokinesis and chemotactic migration of mammalian cells (2008)
  • Author(s): Kato, A., Kurita, S., Hayashi, A., Kaji, N., Ohashi, K.,and Mizuno, K.
  • Journal Title: Biochem.J. 414 Pages: 261-270
• [Journal Article] Cell Adhesion-dependent Cofilin Serine 3 Phosphorylation by the Integrin-linked Kinase・c-Src Complex (2008)
  • Author(s): Kim, Y.B., Choi, S., Choi, M.C., Oh, M.A., Lee, S.A., Cho, M., Mizuno, K., Kim, S.H.,and Lee, J.W.
  • Journal Title: J.Biol.Chem. 283 Pages: 10089-10096
• [Journal Article] Dual regulation of cofilin activity by LIM kinase and Slingshot-1L phosphatase controls Platelet-derived growth factor-induced migration of human aortic smooth muscle cells (2008)
  • Author(s): San Martin, A., Lee, M.Y., Williams, H.C., Mizuno, K., Lassegue, B.,and Griendling, K.K.
  • Journal Title: Circ.Res. 102 Pages: 432-438
• [Journal Article] Cell adhesion-dependent cofilin serine 3 phosphorylation by the integrin-linked kinase・c-Src complex (2008)
  • Author(s): Kim, Y.B., Choi, S., Choi, M.C., Oh, M.A., Lee, S.A., Cho, M., Mizuno, K., Kim, S.H.,and Lee, J.W.
  • Journal Title: J.Biol.Chem. 283 Pages: 10089-10096
• [Journal Article] Suppression of the invasive capacity of rat ascites hepatoma cells by knockdown of Slingshot or LIM-kinase (2008)
  • Author(s): Horita, Y., Ohashi, K., Mukai, M., Inoue, M.,and Mizuno, K.
  • Journal Title: J.Biol.Chem. 283 Pages: 6013-6021
• [Journal Article] LIM-kinase-mediated cofilin phosphorylation during mitosis is required for precise spindle orientation (2008)
  • Author(s): Kaji, N., Muramoto, A., and Mizuno, K.
  • Journal Title: J.Biol.Chem. 283 Pages: 4983-4992
• [Journal Article] TESK1 interacts with Sprouty2 to abrogate its inihibition of Erk phosphorylation downstream of receptor tyrosine kinase signaling (2008)
  • Author(s): Chandramouli, S., Yu, C.Y., Yusoff, P., Lao, D.-H., Leong, H.F., Mizuno, K.,and Guy, G.R.
  • Journal Title: J.Biol.Chem. 283 Pages: 1679-1691
• [Journal Article] Cell Adhesion-dependent Cofilin Serine 3 Phosphorylation by the Integrin-linked Kinasec-Src Complex (2008)
  • Author(s): Kim, Y. B., et.al.
  • Journal Title: J. Biol. Chem. 283 Pages: 10089-10096
  • Peer Reviewed
• [Journal Article] Critical roles of actin-interacting protein 1 in cytokinesis and chemotactic migration of mammalian cells (2008)
  • Author(s): Kato A., et.al.
  • Journal Title: Biochem. J. 414 Pages: 261-270
  • Peer Reviewed
• [Journal Article] Molecular dissection of the mechanisms of substrate recognition and F-actin-mediated activation of cofilin-Dhosnhatase Slingshot-1 (2008)
  • Author(s): Kurita, S., et.al.
  • Journal Title: J. Biol. Chem. 283 Pages: 32542-32552
  • Peer Reviewed
• [Journal Article] TESK1 interacts with Sprouty2 to abrogate its inihibition of Erk phosphorylation downstream of receptor tyrosine kinase signaling. (2008)
  • Author(s): Chandramouli, S., et. al.
  • Journal Title: J. Biol. Chem. 283 Pages: 1679-1691
  • Peer Reviewed
• [Journal Article] LIM-kinase-mediated cofilin phosphorylation during mitosis is required for precise spindle orientation. (2008)
  • Author(s): Kaji, N., et. al.
  • Journal Title: J. Biol. Chem. 283 Pages: 4983-4992
  • Peer Reviewed
• [Journal Article] Suppression of the invasive capacity of rat ascites hepatoma cells by knockdown of Slingshot or LIM-kinase. (2008)
  • Author(s): Horita, Y., et. al.
  • Journal Title: J. Biol. Chem. 283 Pages: 6013-6021
  • Peer Reviewed
• [Journal Article] Cell adhesion-dependent cofilin serine 3 phosphorylation by the integrin-linked kinase/c-Src complex. (2008)
  • Author(s): Kim, Y. B., et. al.
  • Journal Title: J. Biol. Chem. (印刷中)
  • Peer Reviewed
• [Journal Article] Dual regulation of cofilin activity by LIM kinase and Slingshot-1L phosphatase controls Platelet-derived growth factor-induced migration of human aortic smooth muscle cells. (2008)
  • Author(s): San Martin, A., et. al.
  • Journal Title: Circ. Res. 102 Pages: 432-438
  • Peer Reviewed
• [Journal Article] Direct stimulation of receptor-controlled phospholipase D1 by phospho-cofilin (2007)
  • Author(s): Han, L., Stope, M.B., Lopez de Jesus, M., Oude Weernink, P.A., Urban, M., Wieland, T., Rosskopf, D., Mizuno, K., Jakobs, K.H.,and Schmidt, M.
  • Journal Title: EMBO J. 26 Pages: 4189-4202
• [Journal Article] The Slingshot family of phosphatases mediates Rac1 regulation of cofilin phosphorylation, laminin-332 organization and motility behavior of keratinocytes (2007)
  • Author(s): Kligys, K., Claiborne, J.N., DeBiase, P.J., Hopkinson, S.B., Wu, Y., Mizuno, K.,and Jones, J.C.R.
  • Journal Title: J.Biol.Chem. 282 Pages: 32520-32528
• [Journal Article] Synaptic scaffolding molecule alpha is a scaffold to mediate N-methyl-D-aspartate receptor-dependent RhoA activation in dendrites (2007)
  • Author(s): Iida, J, Ishizaki, H, Okamoto-Tanaka, M, Kawata, A, Sumita, K, Ohgake, S, Sato, Y, Yorifuji, H, Nukina, N, Ohashi, K, Mizuno, K, Tsutsumi, T, Mizoguchi, A, Miyoshi, J, Takai, Y,and Hata, Y
  • Journal Title: Mol.Cell.Biol. 27 Pages: 4388-4405
• [Journal Article] Actin filaments-stabilizing and-bundling activities of cofilin-phosphatase Slingshot-1 (2007)
  • Author(s): Kurita, S., Gunji, E., Ohashi, K.,and Mizuno, K.
  • Journal Title: Genes Cells 12 Pages: 663-676
• [Journal Article] LIM-kinase and Slingshot are critical for neurite extension (2007)
  • Author(s): Endo, M., Ohashi, K., Mizuno, K.
  • Journal Title: J.Biol.Chem. 282 Pages: 13692-13702
• [Journal Article] Cofilin promotes stimulus-induced lamellipodium formation by generating an abundant supply of actin monomers (2007)
  • Author(s): Kiuchi, T., Ohashi, K., Kurita, S., Mizuno, K.
  • Journal Title: J.CellBiol. 177 Pages: 465-476
• [Journal Article] Cofilin promotes stimulus-induced lamellipodium formation by generating an abundant supply of actin monomers. (2007)
  • Author(s): Kiuchi, T., et. al.
  • Journal Title: J. Cell Biol. 177 Pages: 465-476
  • Peer Reviewed
• [Journal Article] LIM-kinase and Slingshot are critical for neurite extension. (2007)
  • Author(s): Endo, M., et. al.
  • Journal Title: J. Biol. Chem. 282 Pages: 13692-13702
  • Peer Reviewed
• [Journal Article] Actin filaments-stabilizing and-bundling activities of cofilin-phosphatase Slingshot-1. (2007)
  • Author(s): Kurita, S., et. al.
  • Journal Title: Genes Cells 12 Pages: 663-676
  • Peer Reviewed
• [Journal Article] Synaptic scaffolding molecule alpha is a scaffold to mediate N-methyl-D-aspartate receptor-dependent Rho A activation in dendrites. (2007)
  • Author(s): Iida, J., et. al.
  • Journal Title: Mol. Biol. Cell 27 Pages: 4388-4405
  • Peer Reviewed
• [Journal Article] The slingshot family of phosphatases mediates Racl regulation of cofilin phosphorylation, laminin-332 organization and motility behavior of keratinocytes. (2007)
  • Author(s): Kligys, K., et. al.
  • Journal Title: J. Biol. Chem. 282 Pages: 32520-32528
  • Peer Reviewed
• [Journal Article] Direct stimulation of receptor-controlled phospholipase D1 by phospho-cofilin. (2007)
  • Author(s): Han, L., et. al.
  • Journal Title: EMBO J. 26 Pages: 4189-4202
  • Peer Reviewed
• [Presentation] Wnt-PCP経路による神経突起退縮に関与するRhoA-GEFの同定 (2008)
  • Author(s): 辻拓史, 太田裕作, 大橋一正, 水野健作
  • Organizer: 日本生化学会東北支部例会
  • Place of Presentation: 盛岡
  • Year and Date: 2008-05-17
• [Presentation] Phosphorylation of Slingshot-1 by Polo-like kinase-1 (2008)
  • Author(s): Otsuki, M., Ikebe, C., Ohashi, K., and Mizuno, K.
  • Organizer: The 48th Annual Meeting of The American Society for Cell Biology
  • Place of Presentation: San Francisco
• [Presentation] ラメリポディア形成過程における細胞内G-アクチン濃度のタイムラプスイメージングーDronpa-アクチンのFDAP解析を用いて- (2008)
  • Author(s): 永井友朗、木内泰、大橋一正、水野健作
  • Organizer: BMB2008第81回日本生化学会大会・第31回日本分子生物学会年会・合同大会
  • Place of Presentation: 神戸
• [Presentation] 哺乳類細胞の対称分裂における紡錘体位置決定タンパク質の局在とアクチン骨格の関与 (2008)
  • Author(s): 林文、黒沢豪、梶紀子、大橋一正、鎌倉幸子、住本英樹、水野健作
  • Organizer: BMB2008第81回日本生化学会大会・第31回日本分子生物学会年会・合同大会
  • Place of Presentation: 神戸
• [Presentation] MST2, MST3によるNDR1の活性制御と細胞分裂の制御 (2008)
  • Author(s): 池田真教、千葉秀平、勝沼功吉、大橋一正、水野健作
  • Organizer: BMB2008第81回日本生化学会大会・第31回日本分子生物学会年会・合同大会
  • Place of Presentation: 神戸
• [Presentation] Molecular mechanisms of substrate recognition and F-actin-mediated activation ofcofilin-phosphatase Slingshot-1 and its roles in cell migration and invasion (2008)
  • Author(s): Mizuno, K.
  • Organizer: International Phosphatase Conference
  • Place of Presentation: Maebashi
• [Presentation] Cofilin phospho-regulation plays a critical role in tumor cell motility and invasion (2008)
  • Author(s): Ohashi, K., Horita, Y.,and Mizuno, K.
  • Organizer: 第67回日本癌学会学術総会
  • Place of Presentation: 名古屋
• [Presentation] LIM-kinase is required for BDNF-induced dendritogenesis (2008)
  • Author(s): Miyajima, K., Akatsuka, J., Ohashi, K.,and Mizuno, K.
  • Organizer: 第31回日本神経科学大会
  • Place of Presentation: 東京
• [Presentation] Roles of cofilin phosphorylation in neurite outgrowth and dendritogenesis (2008)
  • Author(s): Ohashi, K., Akatsuka, J., Miyajima, K., Endo, M.,and Mizuno, K.
  • Organizer: 第31回日本神経科学大会ワークショップ
  • Place of Presentation: 東京
• [Presentation] Identification of Rho-GEFs that mediate Dishevelled-induced RhoA activation (2008)
  • Author(s): Tsuji, T., Ohta, Y., Ohashi, K.,and Mizuno, K.
  • Organizer: 第60回日本細胞生物学会大会
  • Place of Presentation: 横浜
• [Presentation] Involvement of cofilin/ADF, Slingshot and LIM-kinase in invadopodium formation of tumor cells (2008)
  • Author(s): Kitatani, K., Horita, Y., Ohashi, K.,and Mizuno, K.
  • Organizer: 第60回日本細胞生物学会大会
  • Place of Presentation: 横浜
• [Presentation] Phosphorylation of Slingshot-1 by Polo-like kinase-1 (2008)
  • Author(s): Otsuki, M., Kaneto, K., Ikebe, C., Ohashi, K.,and Mizuno, K.
  • Organizer: 第60回日本細胞生物学会大会
  • Place of Presentation: 横浜
• [Presentation] Roles of cofilin phospho-regulation in tumor cell migration and invasion (2008)
  • Author(s): Ohashi, K., Horita, Y., Kiuchi, T., Mizuno, K.
  • Organizer: 第60回日本細胞生物学会大会
  • Place of Presentation: 横浜
• [Presentation] Involvement of cofilin/ADF, Slingshot and LIM-kinase in invadopodium tormation a tumor cells (2008)
  • Author(s): Kitatani, K., Horita, Y., Ohashi, K., and Mizuno, K.
  • Organizer: 第60回日本細胞生物学会大会
  • Place of Presentation: 横浜
• [Presentation] Molecular mechanisms of substrate recognition and F-actin-mediated activation of cofilin-phosphatase Slingshot-1 and its roles in cell migration and invasion (2008)
  • Author(s): Mizuno, K.
  • Organizer: International Phosphatase Conference
  • Place of Presentation: Maebashi
• [Presentation] ラメリポディア形成過程における細胞内G・アクチン濃度のタイムラプスイメージング-Dronpa・アクチンのFDAP解析を用いて- (2008)
  • Author(s): 永井友郎、木内泰、橋一正、水野健作
  • Organizer: BMB2008第81回日本生化学会大会・第31回日本分子生物学会年会・合同大会
  • Place of Presentation: 神戸
• [Presentation] Phosphorylation of Slingshot-1 by Polo-like kinase-1 (2008)
  • Author(s): Otguki, M., Ikebe, C., Ohashi, K., and Mizuno, K.
  • Organizer: The 48th Annual Meeting of The American Society for Cell Biology
  • Place of Presentation: San Francisco, USA
• [Presentation] Dronpa融合アクチンを用いた顕微鏡イメージングによるラメリポディア形成におけるコフィリンの機能解析 (2007)
  • Author(s): 木内泰, 大橋一正, 栗田宗一, 水野健作
  • Organizer: 日本生化学会東北支部第73回例会
  • Place of Presentation: 仙台
  • Year and Date: 2007-05-12
• [Presentation] Regulation of cofilin-phosphatase activity of Slingshot-1 by Par-1/MARK3 (2007)
  • Author(s): Mishima, T., Ohta, Y., Ohashi, K.,and Mizuno, K.
  • Organizer: The 47th Annual Meeting of The American Society for Cell Biology
  • Place of Presentation: Washington DC, U.S.A.
• [Presentation] コフィリン脱リン酸化におけるSlingshot-1のN末端領域の機能 (2007)
  • Author(s): 栗田宗一、渡辺陽介、大橋一正、水野健作
  • Organizer: BMB2007(第30回日本分子生物学会年会、第80回日本分子生物学会大会合同大会)
  • Place of Presentation: 横浜
• [Presentation] コフィリンのリン酸化によるラメリポディア内のアクチンターンオーバー制御機構 (2007)
  • Author(s): 大橋一正、藤原佐知子、木内泰、水野健作
  • Organizer: BMB2007(第30回日本分子生物学会年会、第80回日本分子生物学会大会合同大会)
  • Place of Presentation: 横浜
• [Presentation] コフィリンホスファターゼSlingshotの活性化機構とその細胞骨格、細胞運動における機能 (2007)
  • Author(s): 水野健作
  • Organizer: BMB2007(第30回日本分子生物学会年会、第80回日本分子生物学会大会合同大会)ワークショップ
  • Place of Presentation: 横浜
• [Presentation] Critical roles of cofilin/ADF, Slingshot and LIM-kinase in tumor cell invasion (2007)
  • Author(s): Horita, Y., Ohashi, K.,and Mizuno, K.
  • Organizer: 第66回日本癌学会学術総会
  • Place of Presentation: 横浜
• [Presentation] Slingshot regulates primary dendrite formation in rat hippocampal neurons (2007)
  • Author(s): Akatsuka, J., Kiuchi, T., Endo, M., Ohashi, K.,and Mizuno, K.
  • Organizer: Neuro2007
  • Place of Presentation: Yokohama
• [Presentation] Functional roles of cofilin-phosphatase Slingshot in cell migration and tumor cell invasion (2007)
  • Author(s): Kurita, S., Ohashi, K.,and Mizuno, K.
  • Organizer: OLS/NUS-Tohoku COE Joint Symposium
  • Place of Presentation: Singapore
• [Presentation] The role of cofilin in actin filament assembly during lamellipodium formation (2007)
  • Author(s): Kiuchi, T., Ohashi, K., Kurita, S.,and Mizuno, K.
  • Organizer: ELSO 2007
  • Place of Presentation: Dresden, Germany
• [Presentation] Phosphorylation of cofilin regulates actin-based retrograde flow in lamellipodia and lamellipodial length (2007)
  • Author(s): Ohashi, K., Fujiwara, S., Kiuchi, T.,and Mizuno, K.
  • Organizer: 第59回日本細胞生物学会・第40回日本発生生物学会合同大会ワークショップ
  • Place of Presentation: 福岡
• [Presentation] Regulation of cofilin-phosphatase activity of Slingshot-1 by Par-1/MARK3 (2007)
  • Author(s): Mishima, T., Ohta, Y., Ohashi, K.,and Mizuno, K.
  • Organizer: 第59回日本細胞生物学会・第40回日本発生生物学会合同大会
  • Place of Presentation: 福岡
• [Presentation] コフィリンのリン酸化、脱リン酸化制御と細胞運動 (2007)
  • Author(s): 水野健作
  • Organizer: 第7回日本蛋白質科学会年会ワークショップ「生体システムの基盤となる蛋白質の構造変化」
  • Place of Presentation: 仙台
• [Presentation] Regulation of cofilin-phosphatase activity of Slingshot-1 by Par-1/MARK3. (2007)
  • Author(s): Mishima, T., Ohta, Y., Ohashi, K., and Mizuno, K.
  • Organizer: 第59回日本細胞生物学会・第40回日本発生生物学会合同大会
  • Place of Presentation: 福岡
• [Presentation] Phosphorylation of cofilin regulates actin-based retrograde flow in lamellipodia and lamellipodial length. (2007)
  • Author(s): Ohashi, K., Fujiwara, S., Kiuchi, T., and Mizuno, K.
  • Organizer: 第59回日本細胞生物学会・第40回日本発生生物学会合同大会ワークショップ
  • Place of Presentation: 福岡
• [Presentation] The role of cofilin in actin filament assembly during lamellipodium formation. (2007)
  • Author(s): Kiuchi, T., Ohashi, K., Kurita, S., and Mizuno, K.
  • Organizer: ELSO 2007
  • Place of Presentation: Dresden, Germany
• [Presentation] Functional roles of cofilin-phosphatase Slingshot in cell migration and tumor cell invasion. (2007)
  • Author(s): Kurita, S., Ohashi, K., and Mizuno, K.
  • Organizer: OLS/NUS-Tohoku COE Joint Symposium
  • Place of Presentation: Singapore
• [Presentation] Slingshot regulates primary dendrite formation in rat hippocampal neurons. (2007)
  • Author(s): Akatsuka, J., Kiuchi, T., Endo, M., Ohashi, K., and Mizuno, K.
  • Organizer: Neuro 2007
  • Place of Presentation: Yokohama
• [Presentation] Critical roles of cofilin/ADF, Slingshot and LIM-kinase in tumor cell invasion. (2007)
  • Author(s): Horita, Y., Ohashi, K., and Mizuno, K.
  • Organizer: 第66回日本癌学会学術総会
  • Place of Presentation: 横浜
• [Presentation] Regulation of cofilin-phosphatase activity of Slingshot-1 by Par-1/MARK3. (2007)
  • Author(s): Mishima, T., Ohta, Y., Ohashi, K., and Mizuno, K.
  • Organizer: The 47th Annual Meeting of The American Society for Cell Biology
  • Place of Presentation: Washington DC, U.S.A.
• [Book] 生体の科学(細胞骨格、細胞運動、細胞接着を制御するシグナル伝達機構) (2008)
  • Author(s): 栗田宗一、水野健作(分担)
  • Publisher: 医学書院
• [Book] 実験医学増刊(Dronpaを用いたアクチン動態のライブイメージング) (2008)
  • Author(s): 木内泰、水野健作(分担)
  • Publisher: 羊土社
• [Book] 生体の科学(コフィリンを中心としたタンパク質間相互作用) (2007)
  • Author(s): 栗田宗一、水野健作(分担)
  • Publisher: 医学書院