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Signaling mechanism of the apical organelle discharge by malaria parasites during erythrocyte invasion

Research Project

Project/Area Number 19H03461
Research Category

Grant-in-Aid for Scientific Research (B)

Allocation TypeSingle-year Grants
Section一般
Review Section Basic Section 49040:Parasitology-related
Research InstitutionNagasaki University

Principal Investigator

KANEKO Osamu  長崎大学, 熱帯医学研究所, 教授 (50325370)

Co-Investigator(Kenkyū-buntansha) 矢幡 一英  愛媛大学, プロテオサイエンスセンター, 准教授 (40467965)
石崎 隆弘  長崎大学, 熱帯医学研究所, 助教 (40880810)
麻田 正仁  長崎大学, 熱帯医学研究所, 助教 (40587028)
Project Period (FY) 2019-04-01 – 2022-03-31
Project Status Completed (Fiscal Year 2022)
Budget Amount *help
¥17,420,000 (Direct Cost: ¥13,400,000、Indirect Cost: ¥4,020,000)
Fiscal Year 2021: ¥5,200,000 (Direct Cost: ¥4,000,000、Indirect Cost: ¥1,200,000)
Fiscal Year 2020: ¥5,200,000 (Direct Cost: ¥4,000,000、Indirect Cost: ¥1,200,000)
Fiscal Year 2019: ¥7,020,000 (Direct Cost: ¥5,400,000、Indirect Cost: ¥1,620,000)
Keywordsマラリア / 病原性原虫 / 赤血球 / 細胞侵入 / シグナル伝達
Outline of Research at the Start

マラリア原虫の赤血球侵入は原虫の生存に必須であり、ワクチン開発や創薬標的であるが、その分子機序には不明な点が多く、制御手段開発の遅れにつながっている。本研究では、赤血球侵入期に発現する種々の分子を誘導的に欠損させ、侵入中の表現型への影響を検討することで、赤血球侵入の時期に働くシグナル伝達機序を明らかにする。本研究の成果により、分子機能の深い理解に立脚した新たなワクチン構想や創薬が可能となる。

Outline of Final Research Achievements

The main objective of the study was to identify the signaling molecules involved in molecular secretion from the microorganelles of the Plasmodium parasites for erythrocyte invasion. We found that two pseudokinases contribute not only to erythrocyte invasion but also to the exflagellar center formation by the male gametes. We also found that the two diacylglycerol kinases are not essential when each is destroyed, but parasites' viability was severely impaired when destroyed simultaneously. We found that a molecule called APH, which is located downstream of signaling through diacylglycerol kinase, was involved in the secretion of molecules called AMA1 and MTRAP. In the process of video analysis, we also found that merozoites have gliding motility.

Academic Significance and Societal Importance of the Research Achievements

マラリア原虫の赤血球侵入に当たり、細胞内分泌小器官から分泌される種々のワクチン候補抗原の分泌トリガーとそれらをつなぐシグナル伝達に関わる分子を明らかにすることにより、生物学的には、理解が進んでいない赤血球侵入期のシグナル伝達経路の全体像に迫ることができ、明らかとなる分子機能の深い理解に立脚した新たなワクチン構想や創薬が可能となる。特に本研究で見出したメロゾイトの滑走運動は、新たな創薬標的機序となることも期待できる。

Report

(4 results)
  • 2022 Final Research Report ( PDF )
  • 2021 Annual Research Report
  • 2020 Annual Research Report
  • 2019 Annual Research Report
  • Research Products

    (29 results)

All 2022 2021 2020 2019 Other

All Int'l Joint Research (4 results) Journal Article (6 results) (of which Int'l Joint Research: 4 results,  Peer Reviewed: 6 results,  Open Access: 6 results) Presentation (18 results) (of which Int'l Joint Research: 12 results) Remarks (1 results)

  • [Int'l Joint Research] Francis Crick Institute/London Sch Hyg & Trop Med(英国)

    • Related Report
      2021 Annual Research Report
  • [Int'l Joint Research] The Francis Crick Institute(英国)

    • Related Report
      2020 Annual Research Report
  • [Int'l Joint Research] The Francis Crick Institute(英国)

    • Related Report
      2019 Annual Research Report
  • [Int'l Joint Research] NIAID, NIH(米国)

    • Related Report
      2019 Annual Research Report
  • [Journal Article] Distinct effects on the secretion of MTRAP and AMA1 in Plasmodium yoelii following deletion of acylated pleckstrin homology domain-containing protein2022

    • Author(s)
      Nattawat Chaiyawong, Takahiro Ishizaki, Hassan Hakimi, Masahito Asada, Kazuhide Yahata, Osamu Kaneko
    • Journal Title

      Parasitology international

      Volume: 86 Pages: 102479-102479

    • DOI

      10.1016/j.parint.2021.102479

    • NAID

      120007180593

    • Related Report
      2021 Annual Research Report
    • Peer Reviewed / Open Access / Int'l Joint Research
  • [Journal Article] cAMP-dependent protein kinase regulates secretion of apical membrane antigen 1 (AMA1) in Plasmodium yoelii2021

    • Author(s)
      Takahiro Ishizaki, Masahito Asada, Hassan Hakimi, Nattawat Chaiyawong, Yuto Kegawa, Kazuhide Yahatab, Osamu Kaneko
    • Journal Title

      Parasitology international

      Volume: 85 Pages: 102435-102435

    • DOI

      10.1016/j.parint.2021.102435

    • NAID

      120007172255

    • Related Report
      2021 Annual Research Report
    • Peer Reviewed / Open Access
  • [Journal Article] Gliding motility of Plasmodium merozoites2021

    • Author(s)
      Yahata Kazuhide、Hart Melissa N.、Davies Heledd、Asada Masahito、Wassmer Samuel C.、Templeton Thomas J.、Treeck Moritz、Moon Robert W.、Kaneko Osamu
    • Journal Title

      Proceedings of the National Academy of Sciences

      Volume: 118 Issue: 48

    • DOI

      10.1073/pnas.2114442118

    • NAID

      120007188607

    • Related Report
      2021 Annual Research Report
    • Peer Reviewed / Open Access / Int'l Joint Research
  • [Journal Article] A novel Plasmodium yoelii pseudokinase, PypPK1, is involved in erythrocyte invasion and exflagellation center formation2020

    • Author(s)
      Ishizaki Takahiro、Chaiyawong Nattawat、Hakimi Hassan、Asada Masahito、Tachibana Mayumi、Ishino Tomoko、Yahata Kazuhide、Kaneko Osamu
    • Journal Title

      Parasitology International

      Volume: 76 Pages: 102056-102056

    • DOI

      10.1016/j.parint.2020.102056

    • NAID

      120006988309

    • Related Report
      2019 Annual Research Report
    • Peer Reviewed / Open Access
  • [Journal Article] Plasmodium yoelii Erythrocyte-Binding-like Protein Modulates Host Cell Membrane Structure, Immunity, and Disease Severity2020

    • Author(s)
      Peng Yu-chih、Qi Yanwei、Zhang Cui、Yao Xiangyu、Wu Jian、Pattaradilokrat Sittiporn、Xia Lu、Tumas Keyla C.、He Xiao、Ishizaki Takahiro、Qi Chen-Feng、Holder Anthony A.、Myers Timothy G.、Long Carole A.、Kaneko Osamu、Li Jian、Su Xin-zhuan
    • Journal Title

      mBio

      Volume: 11 Issue: 1

    • DOI

      10.1128/mbio.02995-19

    • Related Report
      2019 Annual Research Report
    • Peer Reviewed / Open Access / Int'l Joint Research
  • [Journal Article] A Novel Tool for the Generation of Conditional Knockouts To Study Gene Function across the Plasmodium falciparum Life Cycle2019

    • Author(s)
      Tiburcio Marta、Yang Annie S. P.、Yahata Kazuhide、Suarez-Cortes Pablo、Belda Hugo、Baumgarten Sebastian、van de Vegte-Bolmer Marga、van Gemert Geert-Jan、van Waardenburg Youri、Levashina Elena A.、Sauerwein Robert W.、Treeck Moritz
    • Journal Title

      mBio

      Volume: 10 Issue: 5

    • DOI

      10.1128/mbio.01170-19

    • Related Report
      2019 Annual Research Report
    • Peer Reviewed / Open Access / Int'l Joint Research
  • [Presentation] Secretion of apical membrane antigen 1 (AMA1) is regulated by cAMP-dependent protein kinase in Plasmodium yoelii2021

    • Author(s)
      Kaneko O, Ishizaki T, Asada M, Hakimi H, Chaiyawong N, Kegawa Y, Yahata K
    • Organizer
      第62回日本熱帯医学会大会
    • Related Report
      2021 Annual Research Report
  • [Presentation] cAMP-dependent protein kinase regulates secretion of apical membrane antigen 1 (AMA1) in Plasmodium yoelii2021

    • Author(s)
      Ishizaki T, Asada M, Hakimi H, Chaiyawong N, Kegawa Y, Yahata K, Kaneko O
    • Organizer
      The 19th Awaji International Forum on Infection and Immunity
    • Related Report
      2021 Annual Research Report
    • Int'l Joint Research
  • [Presentation] Acylated pleckstrin homology domain-containing protein (APH) is required for efficient secretion of microneme proteins during erythrocyte invasion by Plasmodium yoelii2021

    • Author(s)
      Chaiyawong N, Ishizaki T, Hakimi H, Asada M, Yahata K, Kaneko O
    • Organizer
      The 19th Awaji International Forum on Infection and Immunity
    • Related Report
      2021 Annual Research Report
    • Int'l Joint Research
  • [Presentation] Phenotypic characterization of Plasmodium yoelii in which a pseudokinase pPK4 is disrupted2021

    • Author(s)
      Too EK, Chaiyawong N, Ishizaki T, Hakimi H, Asada M, Yahata K, Kaneko O
    • Organizer
      The 19th Awaji International Forum on Infection and Immunity
    • Related Report
      2021 Annual Research Report
    • Int'l Joint Research
  • [Presentation] マラリア原虫が有する2種のジアシルグリセロールキナーゼの解析2021

    • Author(s)
      石﨑隆弘、Nattawat Chaiyawong、坂口美亜子、徳舛富由樹、麻田正仁、矢幡一英、金子修
    • Organizer
      第90回日本寄生虫学会大会・第32回日本臨床寄生虫学会合同大会
    • Related Report
      2021 Annual Research Report
  • [Presentation] Erythrocyte-Binding-Like (EBL) protein is the exclusive determinant to explain the difference in the growth speed and the virulence between Plasmodium yoelii 17XL and 17XNL lines2020

    • Author(s)
      Chaiyawong N, Hakimi H, Asada M, Yahata K, Kaneko O
    • Organizer
      Molecular Approach to Malaria 2020
    • Related Report
      2020 Annual Research Report
    • Int'l Joint Research
  • [Presentation] Gliding motility of Plasmodium falciparum merozoites2020

    • Author(s)
      Yahata K, Davies H, Asada M, Templeton TJ, Treeck M, Kaneko O
    • Organizer
      Molecular Approach to Malaria 2020
    • Related Report
      2020 Annual Research Report
    • Int'l Joint Research
  • [Presentation] A novel Plasmodium yoelii pseudokinase, PypPK1, is involved in erythrocyte invasion and exflagellation center formation2020

    • Author(s)
      Ishizaki T, Chaiyawong N, Hakimi H, Asada M, Tachibana M, Ishino T, Yahata K, Kaneko O
    • Organizer
      US-Japan Cooperative Medical Sciences Program: Parasitic Diseases Panel Meeting
    • Related Report
      2020 Annual Research Report
    • Int'l Joint Research
  • [Presentation] ネズミマラリア原虫Plasmodium yoeliiの新規シュードキナーゼ(pPK1)は原虫のexflagellation center (EC)形成に関与する2020

    • Author(s)
      石﨑隆弘、Nattawa Chaiyawong、Hakimi Hassan、麻田正仁、橘真由美、石野智子、矢幡一英、金子修
    • Organizer
      第89回日本寄生虫学会大会
    • Related Report
      2020 Annual Research Report
  • [Presentation] Gliding motility of Plasmodium merozoites.2019

    • Author(s)
      Yahata K
    • Organizer
      National University of Singapore-Nagasaki University Joint Symposium
    • Related Report
      2019 Annual Research Report
    • Int'l Joint Research
  • [Presentation] マラリア原虫メロゾイトの滑走運動2019

    • Author(s)
      矢幡一英, Davies H, 麻田正仁, Templeton T, Treeck M, 金子修
    • Organizer
      第27回分子寄生虫学ワークショップ/第17回分子寄生虫・マラリア研究フォーラム合同大会
    • Related Report
      2019 Annual Research Report
  • [Presentation] ネズミマラリア原虫Plasmodium yoeliiのdiacylglycerol kinase(DAGKp)は赤血球侵入関連分子の表面分泌に関わる2019

    • Author(s)
      石﨑隆弘, 麻田正仁, 徳舛富由樹, 坂口美亜子, 矢幡一英, 金子修
    • Organizer
      第27回分子寄生虫学ワークショップ/第17回分子寄生虫・マラリア研究フォーラム合同大会
    • Related Report
      2019 Annual Research Report
  • [Presentation] Uncovering the mechanism of erythrocyte invasion through phenotypic characterization of undefined malaria parasite proteins for their roles in host cell invasion2019

    • Author(s)
      Suzuki M, Ishizaki T, Asada M, Yahata K, Kaneko O
    • Organizer
      第27回分子寄生虫学ワークショップ/第17回分子寄生虫・マラリア研究フォーラム合同大会
    • Related Report
      2019 Annual Research Report
  • [Presentation] Characterizing actin-binding behaviors of malaria parasite actin depolymerizing factor2019

    • Author(s)
      Suzuki M, Yahata K, Kaneko O, Uyeda TQP
    • Organizer
      The 18th Awaji International Forum on Infection and Immunity
    • Related Report
      2019 Annual Research Report
    • Int'l Joint Research
  • [Presentation] Characterization of a novel Plasmodium yoelii serine threonine kinase related to exflagellation center formation2019

    • Author(s)
      Ishizaki T, Chaiyawong N, Tachibana M, Ishino T, Yahata K, Asada M, Kaneko O
    • Organizer
      The 18th Awaji International Forum on Infection and Immunity
    • Related Report
      2019 Annual Research Report
    • Int'l Joint Research
  • [Presentation] A novel Plasmodium yoelii serine threonine kinase related to exflagellation center formation2019

    • Author(s)
      Ishizaki T, Chaiyawong N, Asada M, Yahata K, Culleton R, Kaneko O
    • Organizer
      30th Annual Molecular Parasitology Meeting
    • Related Report
      2019 Annual Research Report
    • Int'l Joint Research
  • [Presentation] Plasmodium yoelii erythrocyte binding-like protein modulates host cell membrane, immunity and virulence2019

    • Author(s)
      Peng YC, Qi Y, Zhang C, Yao X, Wu J, Lu X, Tumas K, He X, Qi C-F, Holder A, Kaneko O, Myers T, Long C, Li J, Su X
    • Organizer
      The American Society of Tropical Medicine and Hygiene, 68th annual meeting
    • Related Report
      2019 Annual Research Report
    • Int'l Joint Research
  • [Presentation] Erythrocyte Invasion by Malaria Parasites2019

    • Author(s)
      Kaneko O
    • Organizer
      International Joint Forum on Infectious Disease Research 2019
    • Related Report
      2019 Annual Research Report
    • Int'l Joint Research
  • [Remarks] 長崎大学熱帯医学研究所原虫学分野

    • URL

      http://www.tm.nagasaki-u.ac.jp/protozoology/

    • Related Report
      2020 Annual Research Report 2019 Annual Research Report

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Published: 2019-04-18   Modified: 2024-01-30  

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