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Regulation of neuronal ageing through the mTOR signaling by acetylation

Research Project

Project/Area Number 26430072
Research Category

Grant-in-Aid for Scientific Research (C)

Allocation TypeMulti-year Fund
Section一般
Research Field Neurochemistry/Neuropharmacology
Research InstitutionTokai Gakuin University (2015-2017)
Nagasaki University (2014)

Principal Investigator

YASUDA KUNIHIKO  東海学院大学, 健康福祉学部, 准教授(移行) (50278446)

Co-Investigator(Renkei-kenkyūsha) NAGATA Kazuhiro  京都産業大学, 総合生命科学部 生命システム学科, 客員教授 (50127114)
OHYAMA Kyoji  東京医科大学, 大学院医学研究科, 准教授 (00255423)
Research Collaborator NAKAYAMA Yuji  京都薬科大学, 薬学部, 教授 (10280918)
SAITO Yohei  京都薬科大学, 薬学部, 助教 (90411032)
MORI Nozomu  長崎大学, 医歯薬学総合研究科, 教授 (00130394)
Project Period (FY) 2014-04-01 – 2018-03-31
Project Status Completed (Fiscal Year 2017)
Budget Amount *help
¥5,200,000 (Direct Cost: ¥4,000,000、Indirect Cost: ¥1,200,000)
Fiscal Year 2016: ¥2,080,000 (Direct Cost: ¥1,600,000、Indirect Cost: ¥480,000)
Fiscal Year 2015: ¥1,560,000 (Direct Cost: ¥1,200,000、Indirect Cost: ¥360,000)
Fiscal Year 2014: ¥1,560,000 (Direct Cost: ¥1,200,000、Indirect Cost: ¥360,000)
Keywords神経老化 / HDAC6 / Mdm20 / 分子シャペロン / オートファジー / mTOR / Akt / アセチル化修飾 / 老化 / アセチル化 / インスリンシグナル / mTORC2 / Rictor / アクチンリモデリング / ホメオスタシス / 老化制御因子
Outline of Final Research Achievements

Akt/PKA (A kinase) is one of key molecules in insulin signaling, functions in various critical steps in signal transduction for maintaining cellular homeostasis, leading to cell survival and /or longevity. The Akt activity regulates through the phosphorylation by PDK1, under the insulin signaling, and mTORC2/PDK2. Interestingly, in this research, we identified HDAC6 (histone deacetylase) and Mdm20 (an auxiliary subunit of NatB) as the novel regulators of Akt activity. Furthermore, we found that Mdm20 regulates the expression levels of Rictor, one of components of mTORC2 and HDAC6 regulates interaction with each components of mTORC1 and mTORC2. These acetyl-related molecules break through the concept of acetyl modification function in cytoplasm and simultaneously hold promise for the effect of anti-ageing through the regulation of Akt activity under the insulin signaling by in the future.

Report

(5 results)
  • 2017 Annual Research Report   Final Research Report ( PDF )
  • 2016 Research-status Report
  • 2015 Research-status Report
  • 2014 Research-status Report
  • Research Products

    (8 results)

All 2017 2015 2014

All Journal Article (1 results) (of which Peer Reviewed: 1 results,  Open Access: 1 results,  Acknowledgement Compliant: 1 results) Presentation (7 results) (of which Invited: 2 results)

  • [Journal Article] Mdm20 modulates actin remodeling through the mTORC2 pathway via its effect on rictor expression2015

    • Author(s)
      Kunihiko Yasuda, Mayumi Takahashi, Nozomu Mori
    • Journal Title

      PLOS ONE

      Volume: 10 Issue: 11 Pages: e0142943-e0142943

    • DOI

      10.1371/journal.pone.0142943

    • Related Report
      2015 Research-status Report
    • Peer Reviewed / Open Access / Acknowledgement Compliant
  • [Presentation] HDAC6によるHSP105との結合を介したHSP70の機能制御2017

    • Author(s)
      安田邦彦、廣瀬翔、斎藤洋平、森望、中山祐治
    • Organizer
      2017年度生命科学系学会合同年次大会
    • Related Report
      2017 Annual Research Report
  • [Presentation] Mdm20によるmTORC2シグナル制御機構2015

    • Author(s)
      安田邦彦、 森 望
    • Organizer
      BMB2015
    • Place of Presentation
      神戸ポートアイランド
    • Year and Date
      2015-12-01
    • Related Report
      2015 Research-status Report
  • [Presentation] Mdm20によるmTORC2を介した老化作用への効果について2015

    • Author(s)
      安田邦彦、 森 望
    • Organizer
      第38回日本基礎老化学会大会
    • Place of Presentation
      パシフィコ横浜
    • Year and Date
      2015-06-12
    • Related Report
      2015 Research-status Report
  • [Presentation] The poly-glutamine aggregates clearance by acetyl-modification molecules through the pAkt signaling.2015

    • Author(s)
      Kunihiko Yasuda and Nozomu Mori
    • Organizer
      Asian Aging 2015: International Symposium “Asian Aging Core for Longevity (AACL) 2006-2015, 10 years and Beyond”
    • Place of Presentation
      大阪大学中之島センター(大阪府)
    • Year and Date
      2015-03-10 – 2015-03-13
    • Related Report
      2014 Research-status Report
    • Invited
  • [Presentation] Mdm20, a potential regulator for neuronal proteostasis controls mTORC2 activity.2015

    • Author(s)
      Kunihiko Yasuda
    • Organizer
      The 5th Nagasaki-Pusan Joint Seminar on Aging Research
    • Place of Presentation
      長崎大学・ポンペ会館(長崎県)
    • Year and Date
      2015-02-06
    • Related Report
      2014 Research-status Report
    • Invited
  • [Presentation] 初代培養海馬神経細胞におけるHDAC6によるmTORを介したオートファジー誘導シグナル制御機構について2014

    • Author(s)
      安田邦彦、森望
    • Organizer
      第37回日本分子生物学会年会
    • Place of Presentation
      パシフィコ横浜(神奈川県)
    • Year and Date
      2014-11-25 – 2014-11-27
    • Related Report
      2014 Research-status Report
  • [Presentation] N-アセチル化制御関連分子Mdm20によるmTORC2活性制御機構2014

    • Author(s)
      安田邦彦、森望
    • Organizer
      第87回日本生化学会大会
    • Place of Presentation
      国立京都国際会館(京都府)
    • Year and Date
      2014-10-15 – 2014-10-18
    • Related Report
      2014 Research-status Report

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Published: 2014-04-04   Modified: 2019-03-29  

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