• Search Research Projects
  • Search Researchers
  • How to Use
  1. Back to previous page

Physiology and pathology of endocytosis and recycling transport in neurons

Research Project

Project/Area Number 25290024
Research Category

Grant-in-Aid for Scientific Research (B)

Allocation TypePartial Multi-year Fund
Section一般
Research Field Neurochemistry/Neuropharmacology
Research InstitutionTokyo Metropolitan University

Principal Investigator

Hisanaga Shin-ichi  首都大学東京, 理工学研究科, 教授 (20181092)

Co-Investigator(Renkei-kenkyūsha) SAITO TARO  首都大学東京, 大学院理工学研究科, 助教 (70301413)
ASADA AKIKO  首都大学東京, 大学院理工学研究科, 助教 (00336512)
Project Period (FY) 2013-04-01 – 2016-03-31
Project Status Completed (Fiscal Year 2015)
Budget Amount *help
¥17,680,000 (Direct Cost: ¥13,600,000、Indirect Cost: ¥4,080,000)
Fiscal Year 2015: ¥5,070,000 (Direct Cost: ¥3,900,000、Indirect Cost: ¥1,170,000)
Fiscal Year 2014: ¥5,980,000 (Direct Cost: ¥4,600,000、Indirect Cost: ¥1,380,000)
Fiscal Year 2013: ¥6,630,000 (Direct Cost: ¥5,100,000、Indirect Cost: ¥1,530,000)
Keywordsタンパク質 / 酵素 / 神経科学 / 発生・分化 / Cdk5 / LMTK1 / Rab / GRAB / Grab / 老化
Outline of Final Research Achievements

Cdk5 is a brain specific membrane-bound protein kinase. We have analyzed a role of Cdk5 in neurite outgrowth in mouse primary neurons. Cdk5 phosphorylates LMTK1, a novel Ser/Thr kinase in brains, and GRAB, an activator of Rab8. Phosphorylated LMTK1 suppressed activation of Rab11 and phosphorylated GRAB lost the Rab9 activation activity. Rab11 and Rab8 are major regulators in endosome transport, supplying membrane components to the tip of axon or dendrites. Thus, their inactivation results in the reduced neurite outgrowth. This signaling cascade is negative regulatory mechanism of neurite outgrowth.

Report

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

    (37 results)

All 2016 2015 2014 2013 Other

All Int'l Joint Research (2 results) Journal Article (16 results) (of which Int'l Joint Research: 2 results,  Peer Reviewed: 16 results,  Open Access: 6 results,  Acknowledgement Compliant: 6 results) Presentation (15 results) (of which Int'l Joint Research: 2 results,  Invited: 10 results) Book (1 results) Remarks (3 results)

  • [Int'l Joint Research] King's College London(英国)

    • Related Report
      2015 Annual Research Report
  • [Int'l Joint Research] Universidad de Chile(チリ)

    • Related Report
      2015 Annual Research Report
  • [Journal Article] The Abundance of Nonphosphorylated Tau in Mouse and Human Tauopathy Brains Revealed by the Use of Phos-Tag Method2016

    • Author(s)
      Kimura T, Hatsuta H, Masuda-Suzukake M, Hosokawa M, Ishiguro K, Akiyama H, Murayama S, Hasegawa M, Hisanaga S
    • Journal Title

      American Journal of Pathology

      Volume: 186 Issue: 2 Pages: 398-409

    • DOI

      10.1016/j.ajpath.2015.10.009

    • Related Report
      2015 Annual Research Report
    • Peer Reviewed / Open Access
  • [Journal Article] Two degradation pathways of the p35 Cdk5 activation subunit, dependent and independent of ubiquitination.2016

    • Author(s)
      Takasugi et al.,
    • Journal Title

      J. Biol. Chem.

      Volume: 291 Issue: 9 Pages: 4649-4657

    • DOI

      10.1074/jbc.m115.692871

    • Related Report
      2015 Annual Research Report
    • Peer Reviewed / Open Access / Acknowledgement Compliant
  • [Journal Article] Extracellular association of APP and tau fibrils induces intracellular aggregate formation of tau.2015

    • Author(s)
      Takahashi M, Miyata H, Kametani F, Nonaka T, Akiyama H, Hisanaga SI, Hasegawa M.
    • Journal Title

      Acta Neuropathol.

      Volume: 129 Issue: 6 Pages: 895-907

    • DOI

      10.1007/s00401-015-1415-2

    • Related Report
      2015 Annual Research Report
    • Peer Reviewed / Open Access / Int'l Joint Research
  • [Journal Article] Effects of p35 mutations associated with mental retardation on the cellular function of p35-CDK5.2015

    • Author(s)
      Takada et al.,
    • Journal Title

      PLOSONE

      Volume: 10 Issue: 10 Pages: e0140821-e0140821

    • DOI

      10.1371/journal.pone.0140821

    • Related Report
      2015 Annual Research Report
    • Peer Reviewed / Open Access / Int'l Joint Research / Acknowledgement Compliant
  • [Journal Article] LMTK1 regulates dendritic formation by regulating movement of Rab11A-positive endosomes2014

    • Author(s)
      Takano et al
    • Journal Title

      Mol Biol. Cell

      Volume: 25 Issue: 11 Pages: 1755-1768

    • DOI

      10.1091/mbc.e14-01-0675

    • Related Report
      2014 Annual Research Report
    • Peer Reviewed / Acknowledgement Compliant
  • [Journal Article] Valproic acid downregulates Cdk5 activity via transcription of p35 mRNA2014

    • Author(s)
      Takahashi, et al.
    • Journal Title

      Biochem. Biophysic Res Commun.

      Volume: 447 Issue: 4 Pages: 678-682

    • DOI

      10.1016/j.bbrc.2014.04.072

    • Related Report
      2014 Annual Research Report
    • Peer Reviewed / Acknowledgement Compliant
  • [Journal Article] The effect of Cyclin-dependent kinase 5 on voltage-dependent calcium channels in PC12 cells varies according to channel type and cell differentiation state2014

    • Author(s)
      Furusawa et al.,
    • Journal Title

      J. Neurochem

      Volume: 130 Issue: 4 Pages: 498-506

    • DOI

      10.1111/jnc.12746

    • Related Report
      2014 Annual Research Report
    • Peer Reviewed / Acknowledgement Compliant
  • [Journal Article] Preferential targeting of p39-activated Cdk5 to Rac1-induced lamellipodia.2014

    • Author(s)
      Ito, Y., Asada, A., Kobayashi, H., Takano, T., Sharma, G., Saito, T., Ohta, Y., Amano, M., Kaibuchi, K., and Hisanaga, S.
    • Journal Title

      Molecular and Cellular Neurosciences

      Volume: 61 Pages: 34-45

    • DOI

      10.1016/j.mcn.2014.05.006

    • Related Report
      2014 Annual Research Report
    • Peer Reviewed
  • [Journal Article] Physiological and pathological phosphorylation of tau by Cdk52014

    • Author(s)
      Kimura, T., Ishiguro, K., Hisanaga, S.
    • Journal Title

      Frontiers Mol. Neurosci

      Volume: 7 Pages: 65-65

    • DOI

      10.3389/fnmol.2014.00065

    • Related Report
      2014 Annual Research Report
    • Peer Reviewed / Open Access / Acknowledgement Compliant
  • [Journal Article] Cyclin-dependent kinase 5 phosphorylates and induces the degradation of ataxin-22014

    • Author(s)
      Asada, A., Yamazaki, R., Kino, Y., Saito, T., Kimura, T., Miyake, M., Hasegawa, M., Nukina, N. & Hisanaga, S.
    • Journal Title

      Neurosci. Lett.

      Volume: 563 Pages: 112-117

    • DOI

      10.1016/j.neulet.2014.01.046

    • Related Report
      2013 Annual Research Report
    • Peer Reviewed
  • [Journal Article] Phosphorylation of drebrin by cyclin-dependent kinase 5 and its role in neuronal migration.2014

    • Author(s)
      Tanabe et al.
    • Journal Title

      PLOS ONE

      Volume: 9 Issue: 3 Pages: e92291-e92291

    • DOI

      10.1371/journal.pone.0092291

    • Related Report
      2013 Annual Research Report
    • Peer Reviewed / Open Access
  • [Journal Article] LMTK1 regulates dendritic formation by regulating movement of Rab11A-positive endosomes.2014

    • Author(s)
      Takano et al.
    • Journal Title

      Mol. Biol. Cell

      Volume: 25

    • Related Report
      2013 Annual Research Report
    • Peer Reviewed
  • [Journal Article] Isomerase Pin1 Stimulates Dephosphorylation of Tau Protein at Cyclin-dependent Kinase (Cdk5)-dependent Alzheimer Phosphorylation Sites2013

    • Author(s)
      Taeko Kimura, Koji Tsutsumi, Masato Taoka, Taro Saito, Masami Masuda-Suzukake, Koichi Ishiguro, Florian Plattner, Takafumi Uchida, Toshiaki Isobe, Masato Hasegawa, and Shin-ichi Hisanaga
    • Journal Title

      THE JOURNAL OF BIOLOGICAL CHEMISTRY

      Volume: 288 Issue: 11 Pages: 7968-7977

    • DOI

      10.1074/jbc.m112.433326

    • Related Report
      2013 Annual Research Report
    • Peer Reviewed
  • [Journal Article] Dab1-mediated colocalization of multi-adaptor protein CIN85 with Reelin-receptors, ApoER2 or VLDLR, in neurons.2013

    • Author(s)
      T.Fuchigami, Y.Sato1, Y.Tomita1, T.Takano, S.Miyauchi, Y.Tsuchiya, T.Saito, K.Kubo, K.Nakajima, M.Fukuda, M.Hattori, and S.Hisanaga
    • Journal Title

      Genes to Cells

      Volume: in press Issue: 5 Pages: 410-424

    • DOI

      10.1111/gtc.12045

    • Related Report
      2013 Annual Research Report
    • Peer Reviewed
  • [Journal Article] Cyclin I is involved in the regulation of cell cycle progression.2013

    • Author(s)
      Nagano et al.
    • Journal Title

      Cell Cycle

      Volume: 12 Issue: 16 Pages: 2617-2624

    • DOI

      10.4161/cc.25623

    • Related Report
      2013 Annual Research Report
    • Peer Reviewed
  • [Journal Article] Structural basis for the different stability and activity between the Cdk5 complexes with p35 and p39 activators.2013

    • Author(s)
      Saito et al.,
    • Journal Title

      J. Biol. Chem.

      Volume: 288 Issue: 45 Pages: 32433-32439

    • DOI

      10.1074/jbc.m113.512293

    • Related Report
      2013 Annual Research Report
    • Peer Reviewed
  • [Presentation] 軸索伸長に関わる膜供給の新たな制御系―Cdk5によるGRAB(Rab8GEF)のリン酸化はRab8及びRab11を介して軸索伸長を制御する.2015

    • Author(s)
      古澤孝太郎, 淺田明子, 福田光則, 久永眞市.
    • Organizer
      第38回日本分子生物年会第88回日本生化学会大会合同大会
    • Place of Presentation
      神戸、国際会議場
    • Year and Date
      2015-12-01
    • Related Report
      2015 Annual Research Report
  • [Presentation] GRAB, a GEF of Rab8, regulates axonal outgrowth in a Cdk5 phosphorylation-dependent manner.2015

    • Author(s)
      Furusawa, K., Asada, A., Fukuda, M., Hisanaga, S.
    • Organizer
      第58回日本神経化学会大会
    • Place of Presentation
      さいたま市、大宮ソニックシティー
    • Year and Date
      2015-09-11
    • Related Report
      2015 Annual Research Report
  • [Presentation] Phos-tag SDS-PAGE法による神経変性疾患タウのリン酸化解析2015

    • Author(s)
      木村 妙子 久永 眞市
    • Organizer
      日本電気泳動学会
    • Place of Presentation
      東京、東京工科大学
    • Year and Date
      2015-09-04
    • Related Report
      2015 Annual Research Report
    • Invited
  • [Presentation] Reevaluation of physiological and pathological phosphorylation of tau in vitro to human brains2015

    • Author(s)
      Hisanaga, S., Kimura, T
    • Organizer
      25th International Society for Neurochemistry meeting
    • Place of Presentation
      Australia, Cairns
    • Year and Date
      2015-08-23
    • Related Report
      2015 Annual Research Report
    • Int'l Joint Research / Invited
  • [Presentation] Phosphorylation of serotonin 1A receptor (5HT1AR) by Cdk5 activity.2015

    • Author(s)
      Takahashi, M., and Hisanaga, S.
    • Organizer
      25th International Society for Neurochemistry meeting
    • Place of Presentation
      Australia, Cairns
    • Year and Date
      2015-08-23
    • Related Report
      2015 Annual Research Report
    • Int'l Joint Research
  • [Presentation] 脳特異的キナーゼCdk5の活性制御と生理および病理2014

    • Author(s)
      久永眞市
    • Organizer
      第4回メトロポリタン脳の老化・認知症ファーラム
    • Place of Presentation
      東京
    • Year and Date
      2014-12-04
    • Related Report
      2014 Annual Research Report
    • Invited
  • [Presentation] PP1-binding neuronal protein kinase LMTK1 suppresses neurite outgrowth through the regulation of Rab11-dependent endosomal trafficking2014

    • Author(s)
      Hisanaga, S.
    • Organizer
      第11回国際フォスファターゼコンファレンス
    • Place of Presentation
      仙台
    • Year and Date
      2014-11-12 – 2014-11-14
    • Related Report
      2014 Annual Research Report
    • Invited
  • [Presentation] Effect of valproic acid on Cdk5 activity and mouse behavior2014

    • Author(s)
      Takahashi et al
    • Organizer
      第12回アジア太平洋神経化学会
    • Place of Presentation
      高雄(台湾)
    • Year and Date
      2014-08-23 – 2014-08-26
    • Related Report
      2014 Annual Research Report
    • Invited
  • [Presentation] The effect of Cyclin-dependent kinase 5 on voltage-dependent calcium channels in PC12 cells varies according to channel type and cell differentiation state2014

    • Author(s)
      Furusawa et al.
    • Organizer
      第12回アジア太平洋神経化学会
    • Place of Presentation
      高雄(台湾)
    • Year and Date
      2014-08-23 – 2014-08-26
    • Related Report
      2014 Annual Research Report
    • Invited
  • [Presentation] Analysis of tau phosphorylation in Tauopathy using Phos-tag SDS-PAGE.2014

    • Author(s)
      Kimura, T., Hisanaga, S.
    • Organizer
      日本神経病理学会
    • Place of Presentation
      東京
    • Year and Date
      2014-06-05 – 2014-06-07
    • Related Report
      2014 Annual Research Report
    • Invited
  • [Presentation] 神経細胞の軸索と樹状突起形成に関わる新たな膜輸送制御経路Cdk5-LMTK1-Rab112014

    • Author(s)
      久永眞市他
    • Organizer
      第86回日本生化学会大
    • Place of Presentation
      横浜
    • Related Report
      2013 Annual Research Report
    • Invited
  • [Presentation] LMTK1/AATYK1 negatively regulates dendritic arborization of cortical neurons through endosomal trafficking.2013

    • Author(s)
      Takano et al.
    • Organizer
      第24回国際神経化学会
    • Place of Presentation
      メキシコ・カンクン
    • Related Report
      2013 Annual Research Report
    • Invited
  • [Presentation] Regulation of mitochondrial transport and inter-microtubule spacing by Tau phosphorylation at the sites hyperphosphorylated in Alzheimer’s disease.2013

    • Author(s)
      Hisanaga
    • Organizer
      第11回世界生物学的精神医学会国際会議
    • Place of Presentation
      京都
    • Related Report
      2013 Annual Research Report
    • Invited
  • [Presentation] LMTK1 regulates dendritic arborization by regulating movement of Rab11A-positive endosomes.2013

    • Author(s)
      Hisanaga et al.
    • Organizer
      The 43th annual meeting of the Society for Neuroscience.
    • Place of Presentation
      アメリカ・サンディエゴ
    • Related Report
      2013 Annual Research Report
  • [Presentation] 脊髄小脳変性症2型原因タンパク質 Ataxin- 2 の Cdk5 によるリン酸化2013

    • Author(s)
      浅田明子他
    • Organizer
      第56回日本神経化学会大会
    • Place of Presentation
      京都
    • Related Report
      2013 Annual Research Report
  • [Book] 神経細胞におけるCDK5の機能とその異常活性化による神経変性疾患.2013

    • Author(s)
      斎藤太郎、久永眞市
    • Total Pages
      6
    • Publisher
      羊土社
    • Related Report
      2013 Annual Research Report
  • [Remarks] 首都大学東京神経分子機能研究室

    • URL

      http://www.biol.se.tmu.ac.jp/labo.asp?ID=neumol

    • Related Report
      2015 Annual Research Report
  • [Remarks] 神経分子機能研究室

    • URL

      http://www.biol.se.tmu.ac.jp/labo.asp?ID=neumol

    • Related Report
      2014 Annual Research Report
  • [Remarks] 神経分子機能研究室

    • URL

      http://www.biol.se.tmu.ac.jp/labo.asp?ID=neumol

    • Related Report
      2013 Annual Research Report

URL: 

Published: 2013-05-21   Modified: 2022-01-31  

Information User Guide FAQ News Terms of Use Attribution of KAKENHI

Powered by NII kakenhi