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Mechanisms of triggering malaria gametocytogenesis by AP2-G.

Research Project

Project/Area Number 20K07462
Research Category

Grant-in-Aid for Scientific Research (C)

Allocation TypeMulti-year Fund
Section一般
Review Section Basic Section 49040:Parasitology-related
Research InstitutionMie University

Principal Investigator

Kaneko Izumi  三重大学, 医学系研究科, 助教 (20515720)

Project Period (FY) 2020-04-01 – 2023-03-31
Project Status Completed (Fiscal Year 2022)
Budget Amount *help
¥4,290,000 (Direct Cost: ¥3,300,000、Indirect Cost: ¥990,000)
Fiscal Year 2022: ¥1,430,000 (Direct Cost: ¥1,100,000、Indirect Cost: ¥330,000)
Fiscal Year 2021: ¥1,430,000 (Direct Cost: ¥1,100,000、Indirect Cost: ¥330,000)
Fiscal Year 2020: ¥1,430,000 (Direct Cost: ¥1,100,000、Indirect Cost: ¥330,000)
Keywordsマラリア / 転写因子 / ガメトサイト
Outline of Research at the Start

マラリア原虫ガメトサイトは人から蚊への伝播を担う唯一のステージであるが、この無性増殖ステージから有性生殖ステージへの分化の機構は長らく謎であった。しかし最近の転写因子研究により少なくとも3つのAP2 (APETALA2)ファミリー転写因子がこの過程において重要な役割を果たしていることが分ってきた。本研究では3つの転写因子AP2-G, AP2-G2およびAP2-FGを手がかりとして、初期ガメトサイトの形成から雌雄ガメトサイトの分化へと至るガメトサイト形成過程の制御機構を解明することを目的とする。本研究提案の成果は複雑なステージから成るマラリアライフサイクル成立の根本原理解明につながるだろう。

Outline of Final Research Achievements

The target gene and cis-acting element of the transcription factor AP2-G were identified. We found a novel female gametocyte transcription factor AP2-FG2 in the target gene. We found that AP2-FG2 is localized in the nucleus of female gametocytes and binds to the upstream regions of female-specific genes to regulate their gene expression.Furthermore, we found an SNF2-like chromatin remodeling ATPase, gSNF2, which is involved in the differentiation of male gametocytes. The gSNF2-deficient parasites were unable to form normal male gametocytes and completely lost the ability to infection to mosquitoes. We clarified that gSNF2 binds to a specific sequence existing in the upstream region of the male and female gametocyte genes and participates in the gene expression regulation.

Academic Significance and Societal Importance of the Research Achievements

本研究の成果はマラリア原虫の複雑なライフサイクル成立の根本原理の解明の一端を担うものであり、世界的に問題となっているマラリア感染症の予防・治療に繋がると考える。

Report

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

    (5 results)

All 2023 2022 2021

All Journal Article (5 results) (of which Peer Reviewed: 5 results,  Open Access: 3 results)

  • [Journal Article] Plasmodium 6-cysteine proteins determine the commitment of sporozoites to liver-infection2023

    • Author(s)
      Yuda Masao、Kaneko Izumi、Murata Yuho、Iwanaga Shiroh、Okubo Kazuhiro、Nishi Tsubasa
    • Journal Title

      Parasitology International

      Volume: 93 Pages: 102700-102700

    • DOI

      10.1016/j.parint.2022.102700

    • Related Report
      2022 Annual Research Report
    • Peer Reviewed / Open Access
  • [Journal Article] PbAP2-FG2 and PbAP2R-2 function together as a transcriptional repressor complex essential for Plasmodium female development2023

    • Author(s)
      Nishi Tsubasa、Kaneko Izumi、Iwanaga Shiroh、Yuda Masao
    • Journal Title

      PLOS Pathogens

      Volume: 19 Issue: 2 Pages: 1010890-1010890

    • DOI

      10.1371/journal.ppat.1010890

    • Related Report
      2022 Annual Research Report
    • Peer Reviewed / Open Access
  • [Journal Article] Differentiation of Plasmodium male gametocytes is initiated by the recruitment of a chromatin remodeler to a male-specific cis-element2023

    • Author(s)
      Kaneko Izumi, Nishi Tsubasa, Iwanaga Shiroh, Yuda Masao
    • Journal Title

      PNAS

      Volume: -

    • Related Report
      2022 Annual Research Report
    • Peer Reviewed
  • [Journal Article] Identification of a novel AP2 transcription factor in zygotes with an essential role in Plasmodium ookinete development2022

    • Author(s)
      Nishi Tsubasa、Kaneko Izumi、Iwanaga Shiroh、Yuda Masao
    • Journal Title

      PLOS Pathogens

      Volume: 18 Issue: 8 Pages: 1010510-1010510

    • DOI

      10.1371/journal.ppat.1010510

    • Related Report
      2022 Annual Research Report
    • Peer Reviewed / Open Access
  • [Journal Article] Mechanisms of triggering malaria gametocytogenesis by AP2-G2021

    • Author(s)
      Yuda Masao、Kaneko Izumi、Murata Yuho、Iwanaga Shiroh、Nishi Tsubasa
    • Journal Title

      Parasitology International

      Volume: 84 Pages: 102403-102403

    • DOI

      10.1016/j.parint.2021.102403

    • Related Report
      2021 Research-status Report
    • Peer Reviewed

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Published: 2020-04-28   Modified: 2024-01-30  

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