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Mechanisms of cell cycle-dependent primary cilium formation and degradation

Research Project

Project/Area Number 15H04347
Research Category

Grant-in-Aid for Scientific Research (B)

Allocation TypeSingle-year Grants
Section一般
Research Field Functional biochemistry
Research InstitutionTohoku University

Principal Investigator

Mizuno Kensaku  東北大学, 生命科学研究科, 教授 (70128396)

Project Period (FY) 2015-04-01 – 2018-03-31
Project Status Completed (Fiscal Year 2017)
Budget Amount *help
¥16,120,000 (Direct Cost: ¥12,400,000、Indirect Cost: ¥3,720,000)
Fiscal Year 2017: ¥4,680,000 (Direct Cost: ¥3,600,000、Indirect Cost: ¥1,080,000)
Fiscal Year 2016: ¥5,460,000 (Direct Cost: ¥4,200,000、Indirect Cost: ¥1,260,000)
Fiscal Year 2015: ¥5,980,000 (Direct Cost: ¥4,600,000、Indirect Cost: ¥1,380,000)
Keywords一次繊毛 / 細胞周期 / TTBK2 / NDR2 / アクチン / NDR / アクチンダイナミクス / TESK
Outline of Final Research Achievements

Primary cilia are antenna-like sensory organella that transmit various extracellular signals. Primary cilium formation is correlated with the exit from the cell cycle. In this project, we aimed to elucidate the mechanisms underlying cell-cycle-dependent primary cilium formation and obtained several findings as follows: 1) NDR2 localizes to peroxisomes in a manner dependent on the C-terminal GKL sequence, and this localization is required for its function in ciliogenesis. 2) The protein kinase activity of TTBK2 is promoted by the binding of the centrosomal protein Cep164. 3) Jasplakinolide, a potent inducer of actin polymerization, promotes ciliogenesis through cell rounding and YAP inactivation. 4) Glucose deprivation induces ciliogenesis through mTORC1 inactivation and p27KIP1 upregulation. 5) Cep97, a suppressor of primary cilium formation, is degraded upon serum starvation by the ubiquitin-proteasome system.

Report

(4 results)
  • 2017 Annual Research Report   Final Research Report ( PDF )
  • 2016 Annual Research Report
  • 2015 Annual Research Report
  • Research Products

    (20 results)

All 2018 2017 2016 2015 Other

All Journal Article (4 results) (of which Peer Reviewed: 4 results,  Open Access: 2 results,  Acknowledgement Compliant: 1 results) Presentation (15 results) (of which Int'l Joint Research: 2 results,  Invited: 1 results) Remarks (1 results)

  • [Journal Article] Glucose deprivation induces primary cilium formation through mTORC1 inactivation2018

    • Author(s)
      Takahashi, K.、Nagai, T.、Chiba, S.、Nakayama, K.、and Mizuno. K.
    • Journal Title

      J Cell Sci

      Volume: 131 Issue: 1 Pages: 208769-208769

    • DOI

      10.1242/jcs.208769

    • Related Report
      2017 Annual Research Report
    • Peer Reviewed / Open Access
  • [Journal Article] Jasplakinolide induces primary cilium formation through cell rounding and YAP inactivation2017

    • Author(s)
      Nagai, T.、and Mizuno, K.
    • Journal Title

      PLoS One

      Volume: 12 Issue: 8 Pages: e0183030-e0183030

    • DOI

      10.1371/journal.pone.0183030

    • Related Report
      2017 Annual Research Report
    • Peer Reviewed / Open Access
  • [Journal Article] Localization of protein kinase NDR2 to peroxisomes and its role in ciliogenesis.2017

    • Author(s)
      Abe, S., Nagai, T., Masukawa, M., Okumoto, K., Homma, Y., Fujiki, Y., and Mizuno, K.
    • Journal Title

      J. Biol. Chem.

      Volume: 292 Issue: 10 Pages: 4089-4098

    • DOI

      10.1074/jbc.m117.775916

    • Related Report
      2016 Annual Research Report
    • Peer Reviewed / Acknowledgement Compliant
  • [Journal Article] Rabin8 suppresses autophagosome formation independently of its guanine nucleotide-exchange activity toward Rab8.2015

    • Author(s)
      Amagai, Y., Itoh, T., Fukuda, M. and Mizuno, K.
    • Journal Title

      J. Biochem.

      Volume: 印刷中 Issue: 2 Pages: 139-153

    • DOI

      10.1093/jb/mvv032

    • NAID

      40020554105

    • Related Report
      2015 Annual Research Report
    • Peer Reviewed
  • [Presentation] グルコース飢餓ストレスによる一次繊毛形成はmTORC1-p27Kip1 経路を介する2017

    • Author(s)
      高橋 健悟、永井 友朗、水野 健作
    • Organizer
      日本生化学会東北支部 第83回例会
    • Related Report
      2017 Annual Research Report
  • [Presentation] NDR2 のペルオキシソーム膜への局在と一次繊毛形成における役割2017

    • Author(s)
      増川 萌瑛、阿部 彰子、永井 友朗、奥本 寛治、本間 悠太、藤木 幸夫、水野 健作
    • Organizer
      第69回日本細胞生物学会大会
    • Related Report
      2017 Annual Research Report
  • [Presentation] 中心体タンパク質Cep104 の微小管重合活性と一次繊毛形成における役割 Centrosomal protein Cep104 possesses microtubule-polymerizing activity and promotes cilium elongation2017

    • Author(s)
      山添 隆史、梅田 真也、菅谷 優子、永井 友朗、水野 健作
    • Organizer
      第69回日本細胞生物学会大会
    • Related Report
      2017 Annual Research Report
  • [Presentation] mTORC1の不活性化は一次繊毛を促進するが,繊毛の長さを短くする2017

    • Author(s)
      高橋 健悟、永井 友朗、水野 健作
    • Organizer
      第69回日本細胞生物学会大会
    • Related Report
      2017 Annual Research Report
  • [Presentation] 増殖抑制刺激依存的な一次繊毛形成におけるCep97の分解の役割2017

    • Author(s)
      向山 祥帆、永井 友朗、水野 健作
    • Organizer
      第40回日本分子生物学会年会
    • Related Report
      2017 Annual Research Report
  • [Presentation] Cep104は微小管重合活性を持ち一次繊毛の伸長に寄与する2017

    • Author(s)
      山添 隆史、梅田 真也、菅谷 優子、永井 友朗、水野 健作
    • Organizer
      第40回日本分子生物学会年会
    • Related Report
      2017 Annual Research Report
  • [Presentation] Jasplakinolide-induced cell rounding provokes ciliogenesis.2016

    • Author(s)
      T.Nagai, K. Mizuno
    • Organizer
      2016 ASCB Annual Meeting Program
    • Place of Presentation
      The Moscone Center (USA・San Francisco)
    • Year and Date
      2016-12-03
    • Related Report
      2016 Annual Research Report
    • Int'l Joint Research
  • [Presentation] mTORの不活性化を介したグルコース飢餓ストレスによる一次繊毛形成2016

    • Author(s)
      高橋 健悟、永井 友朗、水野 健作
    • Organizer
      第39回日本分子生物学会年会
    • Place of Presentation
      パシフィコ横浜 国立大ホール(神奈川県・横浜市)
    • Year and Date
      2016-11-30
    • Related Report
      2016 Annual Research Report
  • [Presentation] Jasplakinolide induces primary cilium formation via cell rounding and YAP inactivation2016

    • Author(s)
      T.Nagai, K. Mizuno
    • Organizer
      The 28th CDB Meeting, Cilia and Centrosomes: Cilia and Centrosomes: Current Advances and Future Directions
    • Place of Presentation
      多細胞システム形成研究センター (兵庫県・神戸市)
    • Year and Date
      2016-11-27
    • Related Report
      2016 Annual Research Report
    • Int'l Joint Research
  • [Presentation] Jasplakinolide による細胞の球状化はYAP を不活性化し一次繊毛形成を惹起する2016

    • Author(s)
      永井 友朗、水野 健作
    • Organizer
      第68回日本細胞生物学会大会
    • Place of Presentation
      京都テルサ(京都府・京都市)
    • Year and Date
      2016-06-15
    • Related Report
      2016 Annual Research Report
  • [Presentation] FurryはYAPのリン酸化と局在を制御する2015

    • Author(s)
      入江和樹、Alfredo Mateo Torres、永井友朗、水野健作
    • Organizer
      第38回日本分子生物学会年会
    • 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
  • [Presentation] Jasplakinolideによる細胞の球状化は一次繊毛形成を誘導する2015

    • Author(s)
      永井 友朗、高橋 健悟、向山 祥帆、水野健作
    • Organizer
      第38回日本分子生物学会年会
    • 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
  • [Presentation] 増殖抑制シグナル依存的な一次繊毛形成機構2015

    • Author(s)
      水野健作
    • Organizer
      第67回日本細胞生物学会
    • Place of Presentation
      タワーホール船堀(東京都・江戸川区)
    • Year and Date
      2015-06-30
    • Related Report
      2015 Annual Research Report
    • Invited
  • [Presentation] 一次繊毛形成制御キナーゼNDRはC末端GKLモチーフを介してペルオキシソームに局在化する2015

    • Author(s)
      阿部彰子、永井友朗、藤木幸夫、水野健作
    • Organizer
      第67回日本細胞生物学会
    • Place of Presentation
      タワーホール船堀(東京都・江戸川区)
    • Year and Date
      2015-06-30
    • Related Report
      2015 Annual Research Report
  • [Presentation] 細胞増殖抑制時の一次繊毛形成におけるTTBK2キナーゼの機能解析2015

    • Author(s)
      永井友朗、小田聡明、千葉秀平、水野健作
    • Organizer
      日本生化学会東北支部 第81回例会・シンポジウム
    • Place of Presentation
      東北大学さくらホール(宮城県・仙台市)
    • Year and Date
      2015-05-09
    • Related Report
      2015 Annual Research Report
  • [Remarks] 東北大学 大学院生命科学研究科 情報伝達分子解析分野 水野研究室

    • URL

      http://www.biology.tohoku.ac.jp/lab-www/mizuno_lab/

    • Related Report
      2017 Annual Research Report 2016 Annual Research Report 2015 Annual Research Report

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Published: 2015-04-16   Modified: 2019-03-29  

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