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Mechanism of substrate selectivity of gamma-secretase regulated by membrane trafficking

Research Project

Project/Area Number 22790061
Research Category

Grant-in-Aid for Young Scientists (B)

Allocation TypeSingle-year Grants
Research Field Biological pharmacy
Research InstitutionThe University of Tokyo

Principal Investigator

MOROHASHI Yuichi  東京大学, 大学院・薬学系研究科, 助教 (40568169)

Research Collaborator IWATSUBO Takeshi  東京大学, 大学院・医学系研究科, 教授
TOMITA Taisuke  東京大学, 大学院・薬学系研究科, 准教授
Project Period (FY) 2010 – 2011
Project Status Completed (Fiscal Year 2011)
Budget Amount *help
¥4,030,000 (Direct Cost: ¥3,100,000、Indirect Cost: ¥930,000)
Fiscal Year 2011: ¥1,560,000 (Direct Cost: ¥1,200,000、Indirect Cost: ¥360,000)
Fiscal Year 2010: ¥2,470,000 (Direct Cost: ¥1,900,000、Indirect Cost: ¥570,000)
Keywords細胞生物学 / 脳神経疾患 / 薬学 / 酵素 / 小胞輸送
Research Abstract

γ-Secretase is a membrane embedded protease responsible for the production of pathogenic Aβpeptide accumulated in the brains of AD patient, therefore it has been regarded as a promising druggable target for the treatment of AD.γ-Secretase has a number of substrates, so it is crucial to understand its molecular mechanism of substrate selectivety. To this end, we have identified Surf4 that specifically regulates Notch receptor trafficking. Surf4 recognizes the cytosolic portion of Notch receptor and recruits it to the ER-exit site, and regulate its ER-to-Golgi trafficking.

Report

(3 results)
  • 2011 Annual Research Report   Final Research Report ( PDF )
  • 2010 Annual Research Report
  • Research Products

    (13 results)

All 2012 2011 2010 Other

All Journal Article (4 results) (of which Peer Reviewed: 3 results) Presentation (8 results) Remarks (1 results)

  • [Journal Article] Neutralization of Gamma-secretase Activity by Monoclonal Antibody against Extracellular Domain of Nicastrin2012

    • Author(s)
      Hayashi I, Morohashi Y, et al.
    • Journal Title

      Oncogene

      Volume: 31 Pages: 787-798

    • Related Report
      2011 Annual Research Report
    • Peer Reviewed
  • [Journal Article] Phosphorylation and membrane dissociation of the ARF exchange factor GBF1 in mitosis2010

    • Author(s)
      Morohashi Y, et al.
    • Journal Title

      Biochemical Journal

      Volume: 427 Pages: 401-412

    • Related Report
      2010 Annual Research Report
    • Peer Reviewed
  • [Journal Article] Regulation of exosome secretion by Rab35 and its GTPase-activating proteins TBC1D10A-C2010

    • Author(s)
      Hsu C, Morohashi Y, et al.
    • Journal Title

      Journal of Cell Biology

      Volume: 189 Pages: 223-232

    • Related Report
      2010 Annual Research Report
    • Peer Reviewed
  • [Journal Article] アルツハイマー病の分子標的治療法2010

    • Author(s)
      諸橋雄一
    • Journal Title

      日本臨床

      Volume: 68 Pages: 1906-1910

    • Related Report
      2010 Annual Research Report
  • [Presentation] PICALM impacts the production and secretion of Aβ42 in cultured cells2011

    • Author(s)
      Morohashi Y, et al.
    • Organizer
      Neuroscience 2011
    • Place of Presentation
      Washington DC, USA
    • Year and Date
      2011-11-14
    • Related Report
      2011 Annual Research Report
  • [Presentation] Identification and functional analysisof a genetic regulator forγ-secretasesubstrate trafficking2011

    • Author(s)
      一色隼人,山下雄大,石渡智之,諸橋雄一,富田泰輔,岩坪威
    • Organizer
      第30回日本認知症学会学術集会
    • Place of Presentation
      東京
    • Related Report
      2011 Final Research Report
  • [Presentation] Functional analysis of SFT-4 in the C. elegans Notch pathway2011

    • Author(s)
      石渡智之,一色隼人,桑原知樹,諸橋雄一,三谷昌平,富田泰輔,岩坪威
    • Organizer
      第30回日本認知症学会学術集会
    • Place of Presentation
      東京
    • Related Report
      2011 Final Research Report
  • [Presentation] Identification and functional analysisof a genetic regulator forγ-secretasesubstrate trafficking2011

    • Author(s)
      一色隼,山下雄大,石渡智之,諸橋雄一,富田泰輔,岩坪威
    • Organizer
      第6回日本Notch研究会
    • Place of Presentation
      千葉
    • Related Report
      2011 Final Research Report
  • [Presentation] Functional analysis of SFT-4 in the C. elegans Notch pathway2011

    • Author(s)
      石渡智之,一色隼人,桑原知樹,諸橋雄一,三谷昌平,富田泰輔,岩坪威
    • Organizer
      第6回日本Notch研究会
    • Place of Presentation
      千葉
    • Related Report
      2011 Final Research Report
  • [Presentation] Neutralization of Gamma-secretase Activity by Monoclonal Antibody against Extracellular Domain of Nicastrin2010

    • Author(s)
      諸橋雄一
    • Organizer
      The 10th International Congress on Alzheimer's & Parkinson's Diseases
    • Place of Presentation
      Barcelona, Spain
    • Year and Date
      2010-03-11
    • Related Report
      2010 Annual Research Report
  • [Presentation] Functional analysis of SFT-4 in the C. elegans Notch pathway2010

    • Author(s)
      石渡智之,一色隼人,桑原知樹,諸橋雄一,三谷昌平,富田泰輔,岩坪威
    • Organizer
      4^<th> East Asia C. elegans Meeting
    • Place of Presentation
      東京
    • Related Report
      2011 Final Research Report
  • [Presentation] Functional analysis of SFT-4 in the C. elegans Notch pathway2010

    • Author(s)
      石渡智之,一色隼人,桑原知樹,諸橋雄一,三谷昌平,富田泰輔,岩坪威
    • Organizer
      第5回Notch研究会
    • Place of Presentation
      千葉
    • Related Report
      2011 Final Research Report
  • [Remarks] 東京大学大学院薬学系研究科臨床薬学教室HP

    • URL

      http://web.f.u-tokyo.ac.jp/~neuropsc/entranceja.html

    • Related Report
      2011 Final Research Report

URL: 

Published: 2010-08-23   Modified: 2016-04-21  

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