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Possible phosphorylation code for the fibril formation of tau protein

Research Project

Project/Area Number 23651215
Research Category

Grant-in-Aid for Challenging Exploratory Research

Allocation TypeMulti-year Fund
Research Field Living organism molecular science
Research InstitutionKyoto University

Principal Investigator

MORII Takashi  京都大学, エネルギー理工学研究所, 教授 (90222348)

Project Period (FY) 2011 – 2012
Project Status Completed (Fiscal Year 2012)
Budget Amount *help
¥3,900,000 (Direct Cost: ¥3,000,000、Indirect Cost: ¥900,000)
Fiscal Year 2012: ¥1,820,000 (Direct Cost: ¥1,400,000、Indirect Cost: ¥420,000)
Fiscal Year 2011: ¥2,080,000 (Direct Cost: ¥1,600,000、Indirect Cost: ¥480,000)
Keywords活性発現の分子機構 / ペプチド / アミロイド / タウタンパク質 / リン酸化 / 凝集体 / 繊維状凝集体 / アルツハイマー病
Research Abstract

Hyperphosphorylated forms of tau protein are the main component of paired helical filaments (PHFs) of neurofibrillary tangles inthe brain of Alzheimer’s disease patient. However, the detailed mechanisms of how the individual phosphorylation event induces the formation of PHFs remain to beestablished. Tau derived phosphorylated peptides have been utilized to understand the effect of phosphorylation on fibrillation of tau and showed the first example that the position of charged residue plays a critical role for the amyloid fibrillation of tau. We have focused on the fibril-forming sequence of tau, VQIVYK (PHF6), that possesses serine or lysine at its N-terminal in the native isoform of tau, and synthesized the PHF6 derived phosphorylated serine and/or tyrosine containing peptide. Interestingly, the peptide phosphorylated at the N-terminal serine residue showed remarkably low fibrillation propensity as compared to the peptide phosphorylated at tyrosine that possessed the same net-charge. Our results indicate that the role of hyperphosphorylation for the fibril formation of tau should not be considered only from the point of view of altering the net charge of protein. The phosphorylation would afford many variation of tau that could define a "tau-phosphorylation code" for the amyloid-type fibril formation.

Report

(3 results)
  • 2012 Annual Research Report   Final Research Report ( PDF )
  • 2011 Research-status Report
  • Research Products

    (7 results)

All 2013 2012 Other

All Journal Article (2 results) (of which Peer Reviewed: 2 results) Presentation (2 results) Book (2 results) Remarks (1 results)

  • [Journal Article] Positional effects of phosphorylation on the stability and the morphology of tau-related amyloid fibrils2012

    • Author(s)
      Masafumi Inoue、Takashi Konno、Kazuki Tainaka Eiji Nakata Hiro-o Yoshida Takashi Morii
    • Journal Title

      Biochemistry

      Volume: 51巻 Issue: 7 Pages: 1396-1406

    • DOI

      10.1021/bi201451z

    • Related Report
      2012 Final Research Report 2011 Research-status Report
    • Peer Reviewed
  • [Journal Article] Positional effects of phosphorylation on the stability and the morphology of tau-related amyloid fibrils2012

    • Author(s)
      M. Inoue
    • Journal Title

      Biochemistry

      Volume: 51,10 Pages: 1396-1406

    • Related Report
      2012 Annual Research Report
    • Peer Reviewed
  • [Presentation] 2 種類のタウタンパク質凝集性ペプチドによるアミロイド繊維形成の評価2013

    • Author(s)
      馬場 あゆみ、森井 孝
    • Organizer
      日本化学会第93 春季年会
    • Place of Presentation
      立命館大学びわこ・くさつキャンパス
    • Related Report
      2012 Final Research Report
  • [Presentation] 2種類のタウタンパク質凝集性ペプチドによるアミロイド繊維形成の評価2013

    • Author(s)
      馬場 あゆみ(森井 孝)
    • Organizer
      日本化学会第93春季年会
    • Place of Presentation
      立命館大学びわこ・くさつキャンパス
    • Related Report
      2012 Annual Research Report
  • [Book] 「タンパク質ベースの蛍光バイオセンサー」、第8章, 「ここまですすんだバイオセンシング・イメージング」日本化学会編2012

    • Author(s)
      中田栄司、森井 孝
    • Publisher
      化学同人
    • Related Report
      2012 Final Research Report
  • [Book] ここまで進んだバイオセンシング・イメージング2012

    • Author(s)
      中田 栄司
    • Total Pages
      8
    • Publisher
      株式会社化学同人
    • Related Report
      2012 Annual Research Report
  • [Remarks] 研究室ホームページ

    • URL

      http://www.iae.kyoto-u.ac.jp/material/a-12_j.html

    • Related Report
      2012 Final Research Report

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Published: 2011-08-05   Modified: 2019-07-29  

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