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Research on a possible novel transcriptional regulation by a membrane protein

Research Project

Project/Area Number 16K08066
Research Category

Grant-in-Aid for Scientific Research (C)

Allocation TypeMulti-year Fund
Section一般
Research Field Integrative animal science
Research InstitutionHokkaido University

Principal Investigator

Yamaguchi Soichiro  北海道大学, 獣医学研究院, 准教授 (50596864)

Project Period (FY) 2016-04-01 – 2020-03-31
Project Status Completed (Fiscal Year 2019)
Budget Amount *help
¥4,810,000 (Direct Cost: ¥3,700,000、Indirect Cost: ¥1,110,000)
Fiscal Year 2019: ¥1,170,000 (Direct Cost: ¥900,000、Indirect Cost: ¥270,000)
Fiscal Year 2018: ¥1,170,000 (Direct Cost: ¥900,000、Indirect Cost: ¥270,000)
Fiscal Year 2017: ¥1,300,000 (Direct Cost: ¥1,000,000、Indirect Cost: ¥300,000)
Fiscal Year 2016: ¥1,170,000 (Direct Cost: ¥900,000、Indirect Cost: ¥270,000)
KeywordsTMC1 / 転写調節 / 核内移行 / タンパク質切断 / タンパク質分解 / 膜タンパク質 / 生理学
Outline of Final Research Achievements

Transmembrane channel like protein 1 (TMC1) is the mechanoelectrical transduction (MET) channel in hair cells of the inner ear. I found a phenomenon that the cytosolic N-terminal region of overexpressed mouse TMC1 (mTMC1) is localized in nuclei of a small population of HEK293 cells. This suggests that in some cells the N-terminal region of mTMC1 is cleaved and transported into nuclei. In this study, I revealed the positions of the cleavage of overexpressed mTMC1 and the involvement of Importin α in the mechanism of accumulation of the N-terminal region into nuclei. Moreover, overexpression of the N-terminal fragment of mTMC1 changed the expression levels of several genes. These findings suggest the possibility that TMC1 is cleaved and the produced N-terminal fragment regulates transcription in hair cells of the inner ear. However, further investigation is required in order to prove that the transcriptional regulation by mTMC1 happens in vivo.

Academic Significance and Societal Importance of the Research Achievements

本研究成果は、TMC1という膜タンパク質がその切断を介して転写調節を行う可能性があることを示しており、TMC1の内耳有毛細胞での新しい働きの可能性を提示するものである。すなわち、内耳有毛細胞が例えば障害を受けた時など、TMC1の切断減少が起きた時、その遊離したN端領域が核内に移行して、転写調節を行い、有毛細胞機能を変化させる可能性がある。よって、難聴の病態発現の一つの在り方の解明につながる可能性がある成果となる。

Report

(5 results)
  • 2019 Annual Research Report   Final Research Report ( PDF )
  • 2018 Research-status Report
  • 2017 Research-status Report
  • 2016 Research-status Report
  • Research Products

    (2 results)

All 2020 2019

All Presentation (2 results)

  • [Presentation] A cytosolic N-terminal region of Transmembrane Channel-like protein 1 (TMC1) is cleaved and imported into the nucleus in an overexpression system2020

    • Author(s)
      Soichiro Yamaguchi, Maho Kamino, Maho Hamamura, and Ken-ichi Otsuguro
    • Organizer
      第97回日本生理学会大会
    • Related Report
      2019 Annual Research Report
  • [Presentation] TMC1の細胞内N端領域における核移行機序および切断部位の同定2019

    • Author(s)
      神野真帆、濱村眞帆、山口聡一郎、乙黒兼一
    • Organizer
      第162回日本獣医学会学術集会
    • Related Report
      2019 Annual Research Report

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Published: 2016-04-21   Modified: 2021-02-19  

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