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Functional analysis of auxiliary subunits of KCNQ1 channels in the heart

Research Project

Project/Area Number 17K08552
Research Category

Grant-in-Aid for Scientific Research (C)

Allocation TypeMulti-year Fund
Section一般
Research Field General physiology
Research InstitutionJichi Medical University (2018-2020)
Osaka Medical College (2017)

Principal Investigator

NAKAJO Koichi  自治医科大学, 医学部, 教授 (80390699)

Project Period (FY) 2017-04-01 – 2021-03-31
Project Status Completed (Fiscal Year 2020)
Budget Amount *help
¥4,680,000 (Direct Cost: ¥3,600,000、Indirect Cost: ¥1,080,000)
Fiscal Year 2019: ¥1,430,000 (Direct Cost: ¥1,100,000、Indirect Cost: ¥330,000)
Fiscal Year 2018: ¥1,430,000 (Direct Cost: ¥1,100,000、Indirect Cost: ¥330,000)
Fiscal Year 2017: ¥1,820,000 (Direct Cost: ¥1,400,000、Indirect Cost: ¥420,000)
Keywordsイオンチャネル / KCNQ1チャネル / 複合体 / ゼブラフィッシュ / 修飾サブユニット / KCNEタンパク質 / 電気生理学 / イメージング / 心臓 / QT延長症候群 / HCN4チャネル / オプトジェネティクス / 腸管神経 / ゲノム編集 / カリウムチャネル
Outline of Final Research Achievements

To investigate the in vivo functions of KCNQ1 channels, we identified and isolated the KCNQ1 channel ortholog and its auxiliary subunit KCNE orthologs from the zebrafish cDNA library. It turned out that the KCNE3-like gene from zebrafish was a newly-identified KCNE gene. Furthermore, we confirmed that the new KCNE gene works as a KCNQ1 modulator using Xenopus oocytes as an expression system. We are now analyzing the expression and functions of the new KCNE gene in zebrafish. We are also making transgenic zebrafish that express GFP-tagged KCNQ1 and KCNE genes. It is still a work in progress.
Another result we obtained in the project is that we found the mechanism of how KCNE3 modulates KCNQ1 channels. It has been known that KCNE3 makes the KCNQ1 channel constitutively open channel. By taking advantage of the newly-revealed KCNQ1-KCNE3 structure, we identified several critical amino acid residues in the KCNE3 and S1 segment of the KCNQ1 channel.

Academic Significance and Societal Importance of the Research Achievements

KCNQ1は心臓、内耳、腎臓、膵臓、胃腸、気管支の上皮細胞など、体中のあらゆる場所に発現する、生理学的に非常に重要なイオンチャネルである。実際、不整脈、難聴、糖尿病などの疾患との関連が知られている。KCNQ1は体の各部位で異なるKCNEサブユニットと複合体を作っていることがしられており、その発現部位、複合体構成を知ることは、KCNQ1チャネルをターゲットとした創薬研究などにおいて重要な意味を持つ。

Report

(5 results)
  • 2020 Annual Research Report   Final Research Report ( PDF )
  • 2019 Research-status Report
  • 2018 Research-status Report
  • 2017 Research-status Report
  • Research Products

    (13 results)

All 2021 2020 2019 2018 2017

All Journal Article (6 results) (of which Int'l Joint Research: 2 results,  Open Access: 4 results,  Peer Reviewed: 5 results) Presentation (7 results) (of which Int'l Joint Research: 2 results,  Invited: 1 results)

  • [Journal Article] Triad interaction stabilizes the voltage sensor domains in a constitutively open KCNQ1-KCNE3 channel2021

    • Author(s)
      Go Kasuya, Koichi Nakajo
    • Journal Title

      bioRxiv

      Volume: 該当なし

    • DOI

      10.1101/2021.04.05.438515

    • Related Report
      2020 Annual Research Report
    • Open Access
  • [Journal Article] Gastrointestinal Neurons Expressing HCN4 Regulate Retrograde Peristalsis2020

    • Author(s)
      Fujii Kensuke、Nakajo Koichi、Egashira Yoshihiro、Yamamoto Yasuhiro、Kitada Kazuya、Taniguchi Kohei、Kawai Masaru、Tomiyama Hideki、Kawakami Koichi、Uchiyama Kazuhisa、Ono Fumihito
    • Journal Title

      Cell Reports

      Volume: 30 Issue: 9 Pages: 2879-2888

    • DOI

      10.1016/j.celrep.2020.02.024

    • Related Report
      2019 Research-status Report
    • Peer Reviewed / Open Access
  • [Journal Article] Gating modulation of the KCNQ1 channel by KCNE proteins studied by voltage-clamp fluorometry2019

    • Author(s)
      Nakajo Koichi
    • Journal Title

      Biophysics and Physicobiology

      Volume: 16 Issue: 0 Pages: 121-126

    • DOI

      10.2142/biophysico.16.0_121

    • NAID

      130007652558

    • ISSN
      2189-4779
    • Related Report
      2019 Research-status Report
    • Peer Reviewed / Open Access
  • [Journal Article] Analysis of Voltage Sensor Movement in KCNQ1-KCNE1 Channels by Voltage Clamp Fluorometry2018

    • Author(s)
      NAKAJO Koichi
    • Journal Title

      Seibutsu Butsuri

      Volume: 58 Issue: 3 Pages: 144-148

    • DOI

      10.2142/biophys.58.144

    • NAID

      130007378611

    • ISSN
      0582-4052, 1347-4219
    • Related Report
      2018 Research-status Report
    • Peer Reviewed / Open Access
  • [Journal Article] Structural properties determining low K+affinity of the selectivity filter in the TWIK1 K+channel2018

    • Author(s)
      Tsukamoto Hisao、Higashi Masahiro、Motoki Hideyoshi、Watanabe Hiroki、Ganser Christian、Nakajo Koichi、Kubo Yoshihiro、Uchihashi Takayuki、Furutani Yuji
    • Journal Title

      Journal of Biological Chemistry

      Volume: 293 Issue: 18 Pages: 6969-6984

    • DOI

      10.1074/jbc.ra118.001817

    • Related Report
      2017 Research-status Report
    • Peer Reviewed / Int'l Joint Research
  • [Journal Article] Post-translational palmitoylation controls the voltage gating and lipid raft association of the CALHM1 channel.2017

    • Author(s)
      Taruno A, Sun H, Nakajo K, Murakami T, Ohsaki Y, Kido MA, Ono F, Marunaka Y.
    • Journal Title

      Journal of Physiology

      Volume: 595 Issue: 18 Pages: 6121-6145

    • DOI

      10.1113/jp274164

    • Related Report
      2017 Research-status Report
    • Peer Reviewed / Int'l Joint Research
  • [Presentation] ゼブラフィッシュが持つ2つのHCN4チャネルの生物物理学的・薬理学的性質2021

    • Author(s)
      劉嘉瑩、中條浩一
    • Organizer
      第126回日本解剖学会第98回日本生理学会大会合同大会
    • Related Report
      2020 Annual Research Report
  • [Presentation] KCNEサブユニットによるKCNQ1電位センサードメインの制御機構2020

    • Author(s)
      中條 浩一
    • Organizer
      第97回日本生理学会
    • Related Report
      2019 Research-status Report
    • Invited
  • [Presentation] ゼブラフィッシュの3つのROMKチャネルはそれぞれ異なる薬理学的性質を持つ2020

    • Author(s)
      武田悠莉子、小野富三人、中條浩一
    • Organizer
      第97回日本生理学会
    • Related Report
      2019 Research-status Report
  • [Presentation] Determinants of Ba2+ sensitivity in zebrafish ROMK channels2019

    • Author(s)
      Yuriko Takeda, Fumihito Ono, Koichi Nakajo
    • Organizer
      9th FAOPS congress
    • Related Report
      2018 Research-status Report
    • Int'l Joint Research
  • [Presentation] The role of HCN4-positive cells in the gastrointestinal development and motility of zebrafish2019

    • Author(s)
      Fujii Kensuke, Koichi Nakajo, Koichi Kawakami, Yoshihiro Egashira, Yasuhiro Yamamoto, Kohei Tanigushi, Masaru Kawai, Hideki Tomiyama, Kazuhisa Uchiyama, Fumihito Ono
    • Organizer
      9th FAOPS congress
    • Related Report
      2018 Research-status Report
    • Int'l Joint Research
  • [Presentation] Structural basis for the modulation of voltage sensor movement by auxiliary subunits in voltage-gated KCNQ1 channels2018

    • Author(s)
      Koichi Nakajo
    • Organizer
      第95会日本生理学会(高松)
    • Related Report
      2017 Research-status Report
  • [Presentation] Zebrafish possesses three functional ROMK channels with different sensitivities to Ba2+2018

    • Author(s)
      Yuriko Takeda, Fumihito Ono, Koichi Nakajo
    • Organizer
      第95会日本生理学会(高松)
    • Related Report
      2017 Research-status Report

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Published: 2017-04-28   Modified: 2022-01-27  

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