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Elucidation of phosphorylation signal regulating the cell polarity

Research Project

Project/Area Number 25251021
Research Category

Grant-in-Aid for Scientific Research (A)

Allocation TypeSingle-year Grants
Section一般
Research Field Cell biology
Research InstitutionNagoya University

Principal Investigator

Kaibuchi Kozo  名古屋大学, 医学系研究科, 教授 (00169377)

Co-Investigator(Kenkyū-buntansha) 西岡 朋生  名古屋大学, 医学(系)研究科(研究院), 助教 (70435105)
天野 睦紀  名古屋大学, 医学(系)研究科(研究院), 准教授 (90304170)
黒田 啓介  名古屋大学, 医学(系)研究科(研究院), 特任助教 (80631431)
中牟田 信一  名古屋大学, 医学(系)研究科(研究院), 助教 (20647474)
渡辺 崇  名古屋大学, 医学(系)研究科(研究院), 講師 (10402562)
Project Period (FY) 2013-04-01 – 2016-03-31
Project Status Completed (Fiscal Year 2016)
Budget Amount *help
¥46,930,000 (Direct Cost: ¥36,100,000、Indirect Cost: ¥10,830,000)
Fiscal Year 2015: ¥13,520,000 (Direct Cost: ¥10,400,000、Indirect Cost: ¥3,120,000)
Fiscal Year 2014: ¥13,520,000 (Direct Cost: ¥10,400,000、Indirect Cost: ¥3,120,000)
Fiscal Year 2013: ¥19,890,000 (Direct Cost: ¥15,300,000、Indirect Cost: ¥4,590,000)
Keywords細胞内情報伝達 / 細胞極性 / リン酸化 / 質量分析
Outline of Final Research Achievements

The establishment and maintenance of cell polarity is essential to a wide range of biological processes, including axon formation and cell migration. In elucidating of molecular basis of cell polarization, cell polarity proteins such as PAR complex, and Scrib complex have been studied. In these studies, various kinases have been shown to act as cell polarity regulators. However, how these kinases regulate cell polarization is poorly understood. In this study, we used our recently developed proteomic system and identified numerous candidate substrates downstream of polarity-related kinases. Based on the substrate screening results, we analyzed the spatiotemporal dynamics and function of the identified substrates during cell migration. Recently, we also revealed how neurons can grow only a single axon while preventing the formation of unnecessary axons during neuronal polarization.

Report

(4 results)
  • 2016 Final Research Report ( PDF )
  • 2015 Annual Research Report
  • 2014 Annual Research Report
  • 2013 Annual Research Report
  • Research Products

    (39 results)

All 2017 2016 2015 2014 2013 Other

All Journal Article (19 results) (of which Int'l Joint Research: 3 results,  Peer Reviewed: 19 results,  Acknowledgement Compliant: 7 results,  Open Access: 8 results) Presentation (20 results) (of which Int'l Joint Research: 2 results,  Invited: 13 results)

  • [Journal Article] Discovery of Long-Range Inhibitory Signaling to Ensure Single Axon Formation2017

    • Author(s)
      Takano T, Wu M, Nakamuta S, Naoki H, Ishizawa N, Namba T, Watanabe T, Xu C, Hamaguchi T, Yura Y, Amano M, Hahn KM, Kaibuchi K
    • Journal Title

      Nature Communications

      Volume: 印刷中

    • NAID

      120006325188

    • Related Report
      2015 Annual Research Report
    • Peer Reviewed / Acknowledgement Compliant
  • [Journal Article] Phosphorylation Signals in Striatal Medium Spiny Neurons2016

    • Author(s)
      Nagai T, Yoshimoto J, Kannon T, Kuroda K, Kaibuchi K
    • Journal Title

      Trends in Pharmacological Sciences

      Volume: 37 Issue: 10 Pages: 858-71

    • DOI

      10.1016/j.tips.2016.07.003

    • Related Report
      2015 Annual Research Report
    • Peer Reviewed / Acknowledgement Compliant
  • [Journal Article] Focused Proteomics Revealed a Novel Rho-kinase Signaling Pathway in the Heart2016

    • Author(s)
      Yura Y, Amano M, Takefuji M, Bando T, Suzuki K, Kato K, Hamaguchi T, Hasanuzzaman Shohag M, Takano T, Funahashi Y, Nakamuta S, Kuroda K, Nishioka T, Murohara T, Kaibuchi K
    • Journal Title

      Cell Structure and Function

      Volume: 41 Issue: 2 Pages: 105-120

    • DOI

      10.1247/csf.16011

    • NAID

      130005405432

    • ISSN
      0386-7196, 1347-3700
    • Related Report
      2015 Annual Research Report
    • Peer Reviewed / Open Access / Acknowledgement Compliant
  • [Journal Article] PAR3-aPKC regulates Tiam1 by modulating suppressive internal interactions.2016

    • Author(s)
      Matsuzawa, K., Akita, H., Watanabe, T., Kakeno, M., Matsui, T., Wang, S., and Kaibuchi, K.
    • Journal Title

      Mol Biol Cell

      Volume: in press Issue: 9 Pages: 1511-23

    • DOI

      10.1091/mbc.e15-09-0670

    • Related Report
      2015 Annual Research Report
    • Peer Reviewed
  • [Journal Article] Phosphoproteomics of the Dopamine Pathway Enables Discovery of Rap1 Activation as a Reward Signal In Vivo2016

    • Author(s)
      Nagai T, Nakamuta S, Kuroda K, Nakauchi S, Nishioka T, Takano T, Zhang X, Tsuboi D, Funahashi Y, Nakano T, Yoshimoto J, Kobayashi K, Uchigashima M, Watanabe M, Miura M, Nishi A, Kobayashi K, Yamada K, Amano M, Kaibuchi K
    • Journal Title

      Neuron

      Volume: 89 (3) Issue: 3 Pages: 550-65

    • DOI

      10.1016/j.neuron.2015.12.019

    • Related Report
      2015 Annual Research Report
    • Peer Reviewed / Open Access
  • [Journal Article] Radial Glial Cell-Neuron Interaction Directs Axon Formation at the Opposite Side of the Neuron from the Contact Site.2015

    • Author(s)
      Xu, C.;Funahashi, Y.;Watanabe, T.;Takano, T.;Nakamuta, S.;Namba, T.;Kaibuchi, K.
    • Journal Title

      J NEUROSCI

      Volume: 35 Issue: 43 Pages: 14517-14532

    • DOI

      10.1523/jneurosci.1266-15.2015

    • Related Report
      2015 Annual Research Report
    • Peer Reviewed / Int'l Joint Research
  • [Journal Article] TTBK2 with EB1/3 regulates microtubule dynamics in migrating cells through KIF2A phosphorylation.2015

    • Author(s)
      Watanabe, T., Kakeno, M., Matsui, T., Sugiyama, I., Arimura, N., Matsuzawa, K., Shirahige, A., Ishidate, F., Nishioka, T., Taya, S., Hoshino, M., and Kaibuchi, K.
    • Journal Title

      J Cell Biol

      Volume: 210 Issue: 5 Pages: 737-751

    • DOI

      10.1083/jcb.201412075

    • Related Report
      2015 Annual Research Report
    • Peer Reviewed / Open Access
  • [Journal Article] Extracellular and Intracellular Signaling for Neuronal Polarity.2015

    • Author(s)
      Namba, T.;Funahashi, Y.; Nakamuta, S.;Xu, C.;Takano, T.;Kaibuchi, K.
    • Journal Title

      Physiol Rev

      Volume: 95 Issue: 3 Pages: 995-1024

    • DOI

      10.1152/physrev.00025.2014

    • Related Report
      2015 Annual Research Report
    • Peer Reviewed / Open Access / Int'l Joint Research
  • [Journal Article] Phosphoproteomic Analysis Using the WW and FHA Domains as Biological Filters2015

    • Author(s)
      Hasanuzzaman Shohag, M., Nishioka, T., Uddin Ahammad, R., Nakamuta, S., Yura, Y., Hamaguchi, T., Kaibuchi, K., and Amano, M.
    • Journal Title

      Cell Structure and Function

      Volume: 40 Issue: 2 Pages: 95-104

    • DOI

      10.1247/csf.15004

    • NAID

      130005094036

    • ISSN
      0386-7196, 1347-3700
    • Related Report
      2015 Annual Research Report
    • Peer Reviewed
  • [Journal Article] Kinase-interacting substrate screening is a novel method to identify kinase substrates.2015

    • Author(s)
      Amano, M., Hamaguchi, T., Shohag, M. H., Kozawa, K., Kato, K., Zhang, X., Yura, Y., Matsuura, Y., Kataoka, C., Nishioka, T., and Kaibuchi, K.
    • Journal Title

      J Cell Biol

      Volume: 209 Issue: 6 Pages: 895-912

    • DOI

      10.1083/jcb.201412008

    • Related Report
      2015 Annual Research Report
    • Peer Reviewed / Open Access / Acknowledgement Compliant
  • [Journal Article] Neuronal polarization.2015

    • Author(s)
      Takano, T.; Xu, C.; Funahashi, Y.;Namba, T.;Kaibuchi, K.
    • Journal Title

      Development

      Volume: 142 Issue: 12 Pages: 2088-2093

    • DOI

      10.1242/dev.114454

    • NAID

      40021797273

    • Related Report
      2015 Annual Research Report
    • Peer Reviewed / Int'l Joint Research
  • [Journal Article] PAR3 and aPKC regulate Golgi organization through CLASP2 phosphorylation to generate cell polarity.2015

    • Author(s)
      Matsui, T., Watanabe, T., Matsuzawa, K., Kakeno, M., Okumura, N., Sugiyama, I., Itoh, N., and Kaibuchi, K.
    • Journal Title

      Molecular Biology of the Cell

      Volume: 26 Issue: 4 Pages: 751-761

    • DOI

      10.1091/mbc.e14-09-1382

    • Related Report
      2014 Annual Research Report
    • Peer Reviewed
  • [Journal Article] <i>In vivo</i> Screening for Substrates of Protein Kinase A Using a Combination of Proteomic Approaches and Pharmacological Modulation of Kinase Activity2015

    • Author(s)
      Hamaguchi, T., Nakamuta, S., Funahashi, Y., Takano, T., Nishioka, T., Shohag, M.H., Yura, Y., Kaibuchi, K., and Amano, M.
    • Journal Title

      Cell Structure and Function

      Volume: 40 Issue: 1 Pages: 1-12

    • DOI

      10.1247/csf.14014

    • NAID

      130004712922

    • ISSN
      0386-7196, 1347-3700
    • Related Report
      2014 Annual Research Report
    • Peer Reviewed / Acknowledgement Compliant
  • [Journal Article] Developing novel methods to search for substrates of protein kinases such as Rho-kinase2015

    • Author(s)
      Nishioka T, Shohag MH, Amano M, Kaibuchi K
    • Journal Title

      Biochimica et Biophysica Acta

      Volume: - Issue: 10 Pages: 1663-1666

    • DOI

      10.1016/j.bbapap.2015.03.001

    • Related Report
      2014 Annual Research Report
    • Peer Reviewed / Acknowledgement Compliant
  • [Journal Article] Disrupted-in-schizophrenia 1 regulates transport of ITPR1 mRNA for synaptic plasticity.2015

    • Author(s)
      Tsuboi D, Kuroda K, Tanaka M, Namba T, Iizuka Y, Taya S, Shinoda T, Hikita T, Muraoka S, Iizuka M, Nimura A, Mizoguchi A, Shiina N, Sokabe M, Okano H, Mikoshiba K, Kaibuchi K
    • Journal Title

      Nature Neuroscience

      Volume: in press Issue: 5 Pages: 698-707

    • DOI

      10.1038/nn.3984

    • Related Report
      2014 Annual Research Report
    • Peer Reviewed / Acknowledgement Compliant
  • [Journal Article] Neuronal polarization in vivo: Growing in a complex environment.2014

    • Author(s)
      Funahashi, Y., Namba, T., Nakamuta, S., and Kaibuchi, K.
    • Journal Title

      Current opinion in neurobiology

      Volume: 27 Pages: 215-223

    • DOI

      10.1016/j.conb.2014.04.009

    • Related Report
      2014 Annual Research Report
    • Peer Reviewed / Open Access
  • [Journal Article] Plk1 Phosphorylates CLIP-170 and Regulates Its Binding to Microtubules for Chromosome Alignment2014

    • Author(s)
      Kaneko M., Matsuzawa K., Matsui T., Akita H., Sugiyama I., Ishidate F., Nakano A., Takashima S., Goto H., Inagaki M., Kaibuchi K., and Watanabe T.
    • Journal Title

      Cell Structure and Function

      Volume: 39 Issue: 1 Pages: 45-59

    • DOI

      10.1247/csf.14001

    • NAID

      130004053900

    • ISSN
      0386-7196, 1347-3700
    • Related Report
      2013 Annual Research Report
    • Peer Reviewed / Open Access
  • [Journal Article] Pioneering Axons Regulate Neuronal Polarization in the Developing Cerebral Cortex.2014

    • Author(s)
      Namba T, Kibe Y, Funahashi Y, Nakamuta S, Takano T, Ueno T, Shimada A, Kozawa S, Okamoto M, Shimoda Y, Oda K, Wada Y, Masuda T, Sakakibara A, Igarashi M, Miyata T, F-S Catherine, Takeuchi K, Kaibuchi K.
    • Journal Title

      Neuron

      Volume: 81(4) Issue: 4 Pages: 814-829

    • DOI

      10.1016/j.neuron.2013.12.015

    • Related Report
      2013 Annual Research Report
    • Peer Reviewed / Open Access
  • [Journal Article] ERK2-mediated phosphorylation of Par3 regulates neuronal polarization.2013

    • Author(s)
      Yasuhiro Funahashi, Takashi Namba, Shin Fujisue, Norimichi Itoh, Shinichi Nakamuta, Katsuhiro Kato, Akiko Shimada, Chundi Xu, Wei Shan, Tomoki Nishioka, Kozo Kaibuchi
    • Journal Title

      The Journal of Neuroscience

      Volume: 33 Issue: 33 Pages: 13270-13285

    • DOI

      10.1523/jneurosci.4210-12.2013

    • Related Report
      2013 Annual Research Report
    • Peer Reviewed
  • [Presentation] KIOSS法によるPKCのリン酸化基質スクリーニングと その候補分子の解析2016

    • Author(s)
      西岡 朋生
    • Organizer
      第68回日本細胞生物学会・第11回日本ケミカルバイオロジー学会 合同大会
    • Place of Presentation
      京都テルサ(京都府京都市)
    • Year and Date
      2016-06-15
    • Related Report
      2015 Annual Research Report
  • [Presentation] Extracellular and intracellular signaling for neuronal polarity2015

    • Author(s)
      Kozo Kaibuchi
    • Organizer
      EMBO Cortical Neural Development
    • Place of Presentation
      Taipei (Taiwan)
    • Year and Date
      2015-12-04
    • Related Report
      2015 Annual Research Report
    • Int'l Joint Research / Invited
  • [Presentation] 生体内における神経細胞の極性形成機構2015

    • Author(s)
      貝淵 弘三
    • Organizer
      第38回日本分子生物学会年会・第88回日本生化学会大会 合同年会
    • Place of Presentation
      神戸ポートアイランド(兵庫県神戸市)
    • Year and Date
      2015-12-01
    • Related Report
      2015 Annual Research Report
    • Invited
  • [Presentation] Neuronal polarization in vivo: Growing in a complex environment2015

    • Author(s)
      Kozo Kaibuchi
    • Organizer
      EMBO Workshop Cotrical Development in Health and Disease
    • Place of Presentation
      Rehovot (Israel)
    • Year and Date
      2015-04-26
    • Related Report
      2015 Annual Research Report
    • Int'l Joint Research / Invited
  • [Presentation] Neuronal polarization in vivo: growing in a complex environment2015

    • Author(s)
      Kozo Kaibuchi
    • Organizer
      Emerging concepts of the neuronal cytoskeleton (w15-46)
    • Place of Presentation
      Puerto Varas, Chile
    • Year and Date
      2015-03-22 – 2015-03-26
    • Related Report
      2014 Annual Research Report
    • Invited
  • [Presentation] リン酸化セリン・スレオニン結合モチーフを生物学的フィルターとして用いたリン酸化プロテオミクス2014

    • Author(s)
      西岡 朋生
    • Organizer
      第87回日本生化学会大会
    • Place of Presentation
      京都府京都市左京区岩倉大鷺町、国立京都国際会館
    • Year and Date
      2014-10-15 – 2014-10-18
    • Related Report
      2014 Annual Research Report
  • [Presentation] Protein phosphorylation remains as a black box in signal transduction: developing a new method to search for substrates of protein kinases such as Rho-kinase.2014

    • Author(s)
      Kozo Kaibuchi
    • Organizer
      8th International Conference Inhibitors of Protein Kinases (IPK2014)
    • Place of Presentation
      Warsaw, Poland
    • Year and Date
      2014-09-21 – 2014-09-25
    • Related Report
      2014 Annual Research Report
    • Invited
  • [Presentation] Systematic Substrate Screening of Protein Kinases using a Functional Proteomic Approach2014

    • Author(s)
      Mutsuki Amano
    • Organizer
      8th International Conference Inhibitors of Protein Kinases (IPK2014)
    • Place of Presentation
      Warsaw, Poland
    • Year and Date
      2014-09-21 – 2014-09-25
    • Related Report
      2014 Annual Research Report
  • [Presentation] Molecular mechanisms regulating formation, polarity and migration in the developing brain2014

    • Author(s)
      Kozo Kaibuchi
    • Organizer
      12th Meeting of the Asian-Pacific Society for Neurochemistry (APSN)2014
    • Place of Presentation
      Kaohsiung (Ta-Kao), Taiwan
    • Year and Date
      2014-08-23 – 2014-08-26
    • Related Report
      2014 Annual Research Report
    • Invited
  • [Presentation] Protein Phosporylation in Signal transduction2014

    • Author(s)
      Kozo Kaibuchi
    • Organizer
      the 17th World Congress of Basic and Clinical Pharmacology (WCP2014)
    • Place of Presentation
      Cape town, South Africa
    • Year and Date
      2014-07-13 – 2014-07-18
    • Related Report
      2014 Annual Research Report
    • Invited
  • [Presentation] Roles of the Rho Family Gtpases and Related Kinases in Polarized Migration2014

    • Author(s)
      Kozo Kaibuchi
    • Organizer
      GRC (Gordon Research Conference) Signaling by Adhesion Receptors
    • Place of Presentation
      ME(Maine), USA
    • Year and Date
      2014-06-22 – 2014-06-27
    • Related Report
      2014 Annual Research Report
    • Invited
  • [Presentation] Protein phosphorylation remains a black box in signal transduction: Developing a new method to search for substrates of polarity kinases including Rho-kinase2014

    • Author(s)
      Mutsuki Amano
    • Organizer
      The 4th Asia Pacific Protein Association (APPA) Conference
    • Place of Presentation
      Jeju, Korea
    • Year and Date
      2014-05-17 – 2014-05-20
    • Related Report
      2014 Annual Research Report
    • Invited
  • [Presentation] 神経関連キナーゼの基質の網羅的解析2013

    • Author(s)
      天野 睦紀
    • Organizer
      第13回日本蛋白質科学学会年会
    • Place of Presentation
      とりぎん文化会館 (鳥取市)
    • Related Report
      2013 Annual Research Report
  • [Presentation] In vivo Screening of Kinase-Specific Substrates by Phosphatase Inhibitor and Kinase Inhibitor Substrate Screening (PIKISS)2013

    • Author(s)
      西岡 朋生
    • Organizer
      The 25th CDB Meeting Cilia and Centrosomes: from Fertilization to Cancer
    • Place of Presentation
      理研CDB (神戸市)
    • Related Report
      2013 Annual Research Report
  • [Presentation] 質量分析を用いたキナーゼ特異的基質探索法の開発2013

    • Author(s)
      西岡 朋生
    • Organizer
      第65回日本細胞生物学会大会
    • Place of Presentation
      ウインクあいち (名古屋市)
    • Related Report
      2013 Annual Research Report
  • [Presentation] In vivo Screening of Kinase-Specific Substrates by Phosphatase Inhibitor and Kinase Inhibitor Substrate Screening (PIKISS)2013

    • Author(s)
      西岡 朋生
    • Organizer
      HUPO 12th Annual World Congress
    • Place of Presentation
      パシフィコ横浜 (横浜市)
    • Related Report
      2013 Annual Research Report
  • [Presentation] Neuronal polarity in vitro and in vivo

    • Author(s)
      Kozo Kaibuchi
    • Organizer
      International Symposium"Neocortical Organization 2"
    • Place of Presentation
      岡崎コンファレンスセンター (岡崎市)
    • Related Report
      2013 Annual Research Report
    • Invited
  • [Presentation] 蛋白質修飾によるシグナル伝達研究の新展開

    • Author(s)
      貝淵 弘三
    • Organizer
      第13回日本蛋白質科学学会年会
    • Place of Presentation
      とりぎん文化会館 (鳥取市)
    • Related Report
      2013 Annual Research Report
    • Invited
  • [Presentation] Neuronal polarity in vitro and in vivo

    • Author(s)
      Kozo Kaibuchi
    • Organizer
      ASCB2013
    • Place of Presentation
      New orleans, USA
    • Related Report
      2013 Annual Research Report
    • Invited
  • [Presentation] 神経関連キナーゼの基質の網羅的解析

    • Author(s)
      天野 睦紀
    • Organizer
      第27回日本医用マススペクトル学会東海支部講演会
    • Place of Presentation
      名古屋大学医学部 (名古屋市)
    • Related Report
      2013 Annual Research Report
    • Invited

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Published: 2013-05-15   Modified: 2019-07-29  

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