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Spatial and temporal analysis of voltage-sensing phosphatase activity in sperm

Research Project

Project/Area Number 20K07274
Research Category

Grant-in-Aid for Scientific Research (C)

Allocation TypeMulti-year Fund
Section一般
Review Section Basic Section 48020:Physiology-related
Research InstitutionOsaka University

Principal Investigator

Takafumi Kawai  大阪大学, 大学院医学系研究科, 助教 (70614915)

Project Period (FY) 2020-04-01 – 2024-03-31
Project Status Completed (Fiscal Year 2023)
Budget Amount *help
¥4,290,000 (Direct Cost: ¥3,300,000、Indirect Cost: ¥990,000)
Fiscal Year 2022: ¥1,300,000 (Direct Cost: ¥1,000,000、Indirect Cost: ¥300,000)
Fiscal Year 2021: ¥1,300,000 (Direct Cost: ¥1,000,000、Indirect Cost: ¥300,000)
Fiscal Year 2020: ¥1,690,000 (Direct Cost: ¥1,300,000、Indirect Cost: ¥390,000)
Keywords精子 / 膜電位 / VSP
Outline of Research at the Start

申請者はこれまでに、精子が他の細胞種とは異なり独自の膜電位感知機構(電位依存性高k素活性)を有していることを示唆するデータを得ている。しかし上記の膜電位感知機構については未だ不明な点が多く、とりわけ膜電位の感知が精子形成のどの段階で行われるのか、また精子内のどの領域で行われるのか、などの時空間的な詳細は明らかになっていない。本研究ではこの点を明らかにすることで、従来想定されてこなかった膜電位シグナルの新たな側面について明らかにする。

Outline of Final Research Achievements

The study focused on the unique protein VSP, which exhibits enzymatic activity in response to the membrane potential of cells. In the present study, we investigated “when does VSP sense the membrane potential of sperm” and found that the membrane potential information of immature sperm is important. The PIP2 level was analyzed using spermatozoa in different states of maturity, and it was found that VSP activity already occurred in immature spermatozoa. Mutant mice with altered membrane potential sensitivity of VSP showed changes in sperm motility and inositol phospholipid levels, indicating that the potential signaling of immature sperm is important for the formation of the sperm lipid environment.

Academic Significance and Societal Importance of the Research Achievements

これまで我々は、精子において「電気信号を化学信号に変換する」新規の機構が精子の運動性に重要であることを明らかにしていた。このことは、精子に起因する不妊治療などを考えるうえで非常に重要な問題であるが、一方でこれまでVSPがどのタイミングの電気信号を感知しているのかはまったくわかっていなかった。
今回我々は、未成熟精子の電気信号がVSPの活性化に重要であることを初めて明らかにした。また、この点について、実際に精子のVSPの電位感受性を変化させることでも確認した。このことは、精子の電気信号を人為的に制御することで、精子の機能調節も可能になることを示唆しており、重要な知見に繋がることが期待される。

Report

(5 results)
  • 2023 Annual Research Report   Final Research Report ( PDF )
  • 2022 Research-status Report
  • 2021 Research-status Report
  • 2020 Research-status Report
  • Research Products

    (16 results)

All 2024 2023 2022 2021 2020

All Journal Article (12 results) (of which Int'l Joint Research: 4 results,  Peer Reviewed: 12 results,  Open Access: 11 results) Presentation (4 results) (of which Invited: 3 results)

  • [Journal Article] (R)-ketamine restores anterior insular cortex activity and cognitive deficits in social isolation-reared mice2024

    • Author(s)
      Yokoyama Rei、Ago Yukio、Igarashi Hisato、Higuchi Momoko、Tanuma Masato、Shimazaki Yuto、Kawai Takafumi、Seiriki Kaoru、Hayashida Misuzu、Yamaguchi Shun、Tanaka Hirokazu、Nakazawa Takanobu、Okamura Yasushi、Hashimoto Kenji、Kasai Atsushi、Hashimoto Hitoshi
    • Journal Title

      Molecular Psychiatry

      Volume: - Issue: 5 Pages: 1-11

    • DOI

      10.1038/s41380-024-02419-6

    • Related Report
      2023 Annual Research Report
    • Peer Reviewed / Open Access
  • [Journal Article] Glucose absorption activity and gene expression of sugar transporters in the trophotaenia of the viviparous teleost Xenotoca eiseni2023

    • Author(s)
      Iida Atsuo、Tsuda Natsuho、Yoshida Junki、Nomura Jumpei、Ratanayotha Adisorn、Kawai Takafumi、Hondo Eiichi
    • Journal Title

      Biochimica et Biophysica Acta (BBA) - General Subjects

      Volume: 1867 Issue: 11 Pages: 130464-130464

    • DOI

      10.1016/j.bbagen.2023.130464

    • Related Report
      2023 Annual Research Report
    • Peer Reviewed / Int'l Joint Research
  • [Journal Article] Role of K364 next to the active site cysteine in voltage-dependent phosphatase activity of Ci-VSP2023

    • Author(s)
      Paixao Ian Costa、Mizutani Natsuki、Matsuda Makoto、Andriani Rizki Tsari、Kawai Takafumi、Nakagawa Atsushi、Okochi Yoshifumi、Okamura Yasushi
    • Journal Title

      Biophysical Journal

      Volume: - Issue: 11 Pages: 2267-2284

    • DOI

      10.1016/j.bpj.2023.01.022

    • Related Report
      2023 Annual Research Report 2022 Research-status Report
    • Peer Reviewed / Open Access
  • [Journal Article] Insight into the function of a unique voltage-sensor protein (TMEM266) and its short form in mouse cerebellum2022

    • Author(s)
      Kawai T、Narita H、Konno K、Akter S、Andriani RT、Iwasaki H、Nishikawa S、Yokoi N、Fukata Y、Fukata M、Wiriyasermkul P、Kongpracha P、Nagamori S、Takao K、Miyakawa T、Abe M、Sakimura K、Watanabe M、Nakagawa A、Okamura Y
    • Journal Title

      Biochemical Journal

      Volume: 479 Issue: 11 Pages: 1127-1145

    • DOI

      10.1042/bcj20220033

    • Related Report
      2022 Research-status Report
    • Peer Reviewed / Open Access / Int'l Joint Research
  • [Journal Article] Voltage-sensing phosphatase (Vsp) regulates endocytosis-dependent nutrient absorption in chordate enterocytes2022

    • Author(s)
      Ratanayotha Adisorn、Matsuda Makoto、Kimura Yukiko、Takenaga Fumiko、Mizuno Tomoaki、Hossain Md. Israil、Higashijima Shin-ichi、Kawai Takafumi、Ogasawara Michio、Okamura Yasushi
    • Journal Title

      Communications Biology

      Volume: 5 Issue: 1 Pages: 948-948

    • DOI

      10.1038/s42003-022-03916-6

    • Related Report
      2022 Research-status Report
    • Peer Reviewed / Open Access / Int'l Joint Research
  • [Journal Article] Spotlight on the Binding Affinity of Ion Channels for Phosphoinositides: From the Study of Sperm Flagellum2022

    • Author(s)
      Kawai Takafumi、Okamura Yasushi
    • Journal Title

      Frontiers in Physiology

      Volume: 13 Pages: 1-5

    • DOI

      10.3389/fphys.2022.834180

    • Related Report
      2021 Research-status Report
    • Peer Reviewed / Open Access
  • [Journal Article] Heterogeneity of microglial proton channel in different brain regions and its relationship with aging.2021

    • Author(s)
      Kawai T,Takao K,Akter S,Abe M,Sakimura K,Miyakawa T,Okamura Y
    • Journal Title

      J Neurochem.

      Volume: - Issue: 3 Pages: 624-641

    • DOI

      10.1111/jnc.15292

    • Related Report
      2021 Research-status Report 2020 Research-status Report
    • Peer Reviewed / Open Access
  • [Journal Article] Heterologous functional expression of ascidian Nav1 channels and close relationship with the evolutionary ancestor of vertebrate Nav channels2021

    • Author(s)
      Kawai Takafumi、Hashimoto Masaki、Eguchi Natsuki、Nishino Junko M.、Jinno Yuka、Mori-Kreiner Risa、Aspaker Mans、Chiba Daijiro、Ohtsuka Yukio、Kawanabe Akira、Nishino Atsuo S.、Okamura Yasushi
    • Journal Title

      Journal of Biological Chemistry

      Volume: 296 Pages: 100783-100783

    • DOI

      10.1016/j.jbc.2021.100783

    • Related Report
      2021 Research-status Report
    • Peer Reviewed / Open Access / Int'l Joint Research
  • [Journal Article] Engineering an enhanced voltage-sensing phosphatase2020

    • Author(s)
      Kawanabe Akira、Mizutani Natsuki、Polat Onur K.、Yonezawa Tomoko、Kawai Takafumi、Mori Masayuki X.、Okamura Yasushi
    • Journal Title

      Journal of General Physiology

      Volume: 152 Issue: 5

    • DOI

      10.1085/jgp.201912491

    • Related Report
      2020 Research-status Report
    • Peer Reviewed / Open Access
  • [Journal Article] TRPM5 Negatively Regulates Calcium-Dependent Responses in Lipopolysaccharide-Stimulated B Lymphocytes2020

    • Author(s)
      Sakaguchi Taiki、Okumura Ryu、Ono Chisato、Okuzaki Daisuke、Kawai Takafumi、Okochi Yoshifumi、Tanimura Natsuko、Murakami Mari、Kayama Hisako、Umemoto Eiji、Kioka Hidetaka、Ohtani Tomohito、Sakata Yasushi、Miyake Kensuke、Okamura Yasushi、Baba Yoshihiro、Takeda Kiyoshi
    • Journal Title

      Cell Reports

      Volume: 31 Issue: 10 Pages: 107755-107755

    • DOI

      10.1016/j.celrep.2020.107755

    • Related Report
      2020 Research-status Report
    • Peer Reviewed / Open Access
  • [Journal Article] The Slo3/Lrrc52 complex is sensitive to phosphoinositides2020

    • Author(s)
      Kawai Takafumi、Okamura Yasushi
    • Journal Title

      Channels

      Volume: 14 Issue: 1 Pages: 190-192

    • DOI

      10.1080/19336950.2020.1778393

    • Related Report
      2020 Research-status Report
    • Peer Reviewed / Open Access
  • [Journal Article] Regulation of hepatic oxidative stress by voltage‐gated proton channels (Hv1/VSOP) in Kupffer cells and its potential relationship with glucose metabolism2020

    • Author(s)
      Kawai Takafumi、Kayama Kento、Tatsumi Shoki、Akter Sharmin、Miyawaki Nana、Okochi Yoshifumi、Abe Manabu、Sakimura Kenji、Yamamoto Hiroyasu、Kihara Shinji、Okamura Yasushi
    • Journal Title

      The FASEB Journal

      Volume: 34 Issue: 12 Pages: 15805-15821

    • DOI

      10.1096/fj.202001056rrr

    • Related Report
      2020 Research-status Report
    • Peer Reviewed / Open Access
  • [Presentation] Voltage-sensing Phosphatase (VSP) Activity in Mammalian Epididymal Maturating Spermatozoa2024

    • Author(s)
      河合喬文
    • Organizer
      第101回日本生理学会大会
    • Related Report
      2023 Annual Research Report
  • [Presentation] Function of calcium-activated ion channels in medial habenula neurons2023

    • Author(s)
      河合喬文
    • Organizer
      第46回日本神経科学大会
    • Related Report
      2023 Annual Research Report
    • Invited
  • [Presentation] Ion channel regulation by phosphoinositides phosphatase and its voltage-dependence in mice sperm flagellum2023

    • Author(s)
      Takafumi Kawai
    • Organizer
      日本生理学会 第100回記念大会
    • Related Report
      2022 Research-status Report
    • Invited
  • [Presentation] 電位依存性ホスファターゼによる精子鞭毛におけるイノシトールリン脂質極性形成とそのメカニズム2021

    • Author(s)
      河合喬文
    • Organizer
      第126回日本解剖学会総会・全国学術集会 / 第98回日本生理学会大会 合同大会
    • Related Report
      2020 Research-status Report
    • Invited

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Published: 2020-04-28   Modified: 2025-01-30  

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