Analysis of molecular mechanism of trogocytosis in Entamoeba histolytica

• Project/Area Number: 18H02650
• Research Category: Grant-in-Aid for Scientific Research (B)
• Allocation Type: Single-year Grants
• Section: 一般
• Review Section: Basic Section 49040:Parasitology-related
• Research Institution: The University of Tokyo
• Principal Investigator: Nozaki Tomoyoshi 東京大学, 大学院医学系研究科(医学部), 教授 (60198588)
• Co-Investigator(Kenkyū-buntansha): Jeelani Ghulam 東京大学, 大学院医学系研究科(医学部), 助教 (60468519)
• Project Period (FY): 2018-04-01 – 2021-03-31
• Project Status: Completed (Fiscal Year 2020)
• Budget Amount: ¥17,160,000 (Direct Cost: ¥13,200,000、Indirect Cost: ¥3,960,000); Fiscal Year 2020: ¥5,590,000 (Direct Cost: ¥4,300,000、Indirect Cost: ¥1,290,000); Fiscal Year 2019: ¥5,850,000 (Direct Cost: ¥4,500,000、Indirect Cost: ¥1,350,000); Fiscal Year 2018: ¥5,720,000 (Direct Cost: ¥4,400,000、Indirect Cost: ¥1,320,000)
• Keywords: 赤痢アメーバ / 腸炎 / 貪食 / 病原機構 / 受容体 / キナーゼ / フォスファターゼ / 脂質輸送 / 貧食

Outline of Final Research Achievements

Engulfment is categorized into two modes: phagocytosis and trogocytosis. The objective of this study was to elucidate molecular mechanisms involved in trogocytosis in the enteric protozoan parasite Entamoeba histoltyica. The putative parasite's receptor for the attachment of the target human cells was identified. A phosphatase that catalyzes phosphatidylinositol 3,4,5-triphosphates was found to be involved in the regulation of trogycytosis. In addition, a lipid transfer protein involved in the transport of phosphatidylinositol phosphates was identified.

Academic Significance and Societal Importance of the Research Achievements

赤痢アメーバによる腸炎・赤痢は海外では年間に世界人口の約1%が感染するとされている重要な感染症である。日本国内でも年間1000例を超える届け出のある最多の寄生虫症である。赤痢アメーバの病原機構の中心を占める咀嚼食に直接関与する分子を同定し、その詳細な働き方を理解することにより、今後赤痢アメーバの起こす病気の理解が進むと同時に、新しい治療法や予防法を作り出すことが出来る可能性が示された。

Research Products

• [Int'l Joint Research] Jamia Islamia大学(インド)
• [Int'l Joint Research] Jamia Islamia大学(インド)
• [Journal Article] Two StAR-related lipid transfer proteins play specific roles in endocytosis, exocytosis, and motility in the parasitic protist Entamoeba histolytica. (2021)
  • Author(s): Das, K., Watanabe, N., and Nozaki, T.
  • Journal Title: PLoS Pathog Volume: In press
  • Peer Reviewed / Open Access / Int'l Joint Research
• [Journal Article] Diversity of phosphoinositide binding proteins in Entamoeba histolytica. (2021)
  • Author(s): Watanabe, N., Nakada-Tsukui, K., and Nozaki, T.
  • Journal Title: Parasitol Int Volume: In press
  • Peer Reviewed / Open Access
• [Journal Article] Rab7D small GTPase is involved in phago‐, trogocytosis and cytoskeletal reorganization in the enteric protozoan Entamoeba histolytica (2020)
  • Author(s): Saito‐Nakano Yumiko、Wahyuni Ratna、Nakada‐Tsukui Kumiko、Tomii Kentaro、Nozaki Tomoyoshi
  • Journal Title: Cellular Microbiology Volume: 23 Issue: 1
  • DOI: 10.1111/cmi.13267
  • Peer Reviewed / Open Access
• [Journal Article] Import of Entamoeba histolytica mitosomal ATP sulfurylase relies on internal targeting sequences. Special Issue “Virulence and Parasitism of Parasitic Protozoa” (2020)
  • Author(s): Santos, H. J., Chiba, Y., Makiuchi, T., Arakawa, S., Murakami, Y., Tomii, K., Imai, K., Nozaki, T.
  • Journal Title: Microorganisms Volume: 8 Issue: 8 Pages: 1229-1229
  • DOI: 10.3390/microorganisms8081229
  • Peer Reviewed / Open Access
• [Journal Article] A lysosomal hydrolase receptor, CPBF2, is associated with motility and invasion of the enteric protozoan parasite Entamoeba histolytica (2020)
  • Author(s): Nakada-Tsukui Kumiko、Marumo Konomi、Nozaki Tomoyoshi
  • Journal Title: Molecular and Biochemical Parasitology Volume: 239 Pages: 111299-111299
  • DOI: 10.1016/j.molbiopara.2020.111299
  • Peer Reviewed / Open Access
• [Journal Article] Dynamism of PI4-Phosphate during Interactions with Human Erythrocytes in Entamoeba histolytica (2020)
  • Author(s): Watanabe Natsuki、Nakada-Tsukui Kumiko、Maehama Tomohiko、Nozaki Tomoyoshi
  • Journal Title: Microorganisms Volume: 8 Issue: 7 Pages: 1050-1050
  • DOI: 10.3390/microorganisms8071050
  • Peer Reviewed / Open Access
• [Journal Article] The emerging role of trogocytosis in the evasion of cancers and parasitic protists from immune cells (2020)
  • Author(s): Nakada-Tsukui Kumiko、Nozaki Tomoyoshi
  • Journal Title: Biotarget Volume: 4 Pages: 4-4
  • DOI: 10.21037/biotarget.2020.03.02
  • Peer Reviewed / Open Access
• [Journal Article] Two isotypes of phosphatidylinositol 3‐phosphate ‐ binding sorting nexins play distinct roles in trogocytosis in Entamoeba histolytica (2019)
  • Author(s): Watanabe Natsuki、Nakada‐Tsukui Kumiko、Nozaki Tomoyoshi
  • Journal Title: Cellular Microbiology Volume: 22 Issue: 3 Pages: 1-16
  • DOI: 10.1111/cmi.13144
  • Peer Reviewed / Open Access
• [Journal Article] Genome-wide analysis of known and potential tetraspanins in Entamoeba histolytica. (2019)
  • Author(s): Tomii, K., Santos, H. J., and Nozaki, T.
  • Journal Title: Genes (Basel), Microbial Genetics and Genomics Volume: 10(11) Issue: 11 Pages: 885-885
  • DOI: 10.3390/genes10110885
  • Peer Reviewed / Open Access
• [Journal Article] An Entamoeba-Specific Mitosomal Membrane Protein with Potential Association to the Golgi Apparatus. (2019)
  • Author(s): Santos, H.J., Hanadate, Y., Imai, K., Nozak, T.
  • Journal Title: Genes Volume: 10 Issue: 5 Pages: 367-367
  • DOI: 10.3390/genes10050367
  • Peer Reviewed / Open Access
• [Journal Article] Phosphatidylinositol Kinases and Phosphatases in Entamoeba histolytica (2019)
  • Author(s): Nakada-Tsukui Kumiko、Watanabe Natsuki、Maehama Tomohiko、Nozaki Tomoyoshi
  • Journal Title: Frontiers in Cellular and Infection Microbiology Volume: 9 Pages: 150-150
  • DOI: 10.3389/fcimb.2019.00150
  • NAID: 120006649617
  • Peer Reviewed / Open Access
• [Journal Article] Novel lineage-specific transmembrane β-barrel proteins in the endoplasmic reticulum of Entamoeba histolytica (2019)
  • Author(s): Santos HJ, Imai K, Makiuchi T, Tomii K, Horton P, Nozawa A, Okada K, Tozawa Y, Nozaki T
  • Journal Title: FEBS J Volume: 印刷中 Issue: 17 Pages: 3416-3432
  • DOI: 10.1111/febs.14870
  • Peer Reviewed / Open Access
• [Presentation] Host modulation by excreted proteins from the extracellular intestinal parasite. Plenary lecture in Bridging Session. (2020)
  • Author(s): Nozaki, T.
  • Organizer: The 16th International Congress of Bacteriology and Applied Microbiology and 16th Internationa Congress of Mycology and Eukaryotic Microbiology and 18th International Congress of Virology, IUMS2020
  • Int'l Joint Research / Invited
• [Presentation] Drug discovery against malaria and amebiasis using natural bioresources and chemical libraries. United States-Japan Cooperative Medical Science Program. (2020)
  • Author(s): Nozaki, T.
  • Organizer: The 50th Joint Conference on Parasitic Diseases
• [Presentation] Pathogenesis of amebiasis and drug development against parasitic diseases using microbial megabiodiversity. Departmento of Microbiology & Immunology Programme Seminar Series. (2020)
  • Author(s): Nozaki, T.
  • Organizer: National University of Singapore
  • Int'l Joint Research / Invited
• [Presentation] Phosphatidylinositol kinases and phosphatases in the enteric protozoan parasite Entamoeba histolytica. (2019)
  • Author(s): Kumiko Nakada-Tsukui, Natsuki Watanabe, Tomoo Maehama, Tomoyoshi Nozaki.
  • Organizer: ASCB|EMBO 2019 meeting
  • Int'l Joint Research
• [Presentation] Drug development against tropical infectious diseases using natural bioresources. (2019)
  • Author(s): Nozaki, T.
  • Organizer: ICMR-DST-AMED Workshop for India-Japan Collaboration
  • Int'l Joint Research
• [Presentation] Atg8 is differentially recruited to two types of phagosomes in the enteric protozoan parasite Entamoeba histolytica. (2019)
  • Author(s): Kumiko Nakada-Tsukui, Kumiko Shibata, Tomoyoshi Nozaki.
  • Organizer: the 9th international symposium on autophagy
  • Int'l Joint Research
• [Presentation] Two isotypes of phosphatidylinositol 3-phosphate-binding sorting nexins play distinct roles in trogocytosis in Entamoeba histolytica. Eukaryome impact on Intestine homeostasis and mucosal immunology. (2019)
  • Author(s): Watanabe, N., Nakada-Tsukui, K., and Nozaki, T.
  • Organizer: Institut Pasteur
  • Int'l Joint Research
• [Presentation] What determines trogocytosis and phagocytosis? Eukaryome impact on Intestine homeostasis and mucosal immunology. (2019)
  • Author(s): Nakada-Tsukui, K., Suzuki, M., and Nozaki, T.
  • Organizer: Institut Pasteur
  • Int'l Joint Research
• [Presentation] Biochemical, structural and functional characterization of glycerol kinase from human enteric protozoan parasite Entamoeba histolytica. (2019)
  • Author(s): Nozaki, T and Jeelani G.
  • Organizer: 第92回日本生化学会大会 シンポジウム 構造生物学から見た寄生適応の分子戦略
• [Presentation] A novel parasite-secreted lysine and glutamic acid rich protein 2 from Entamoeba histolytica infiltrates the host nucleus and regulates the host-parasite interaction. (2019)
  • Author(s): Tomoyoshi Nozaki, Koushik Das.
  • Organizer: VIII European Congress of Protistology (ECOP)
  • Int'l Joint Research
• [Presentation] A lineage-specific mitosomal membrane protein possibly involved in mitosome-endosome membrane contact site in Entamoeba histolytica. (2019)
  • Author(s): Herbert J. Santos, Yuki Hanadate, Kenichiro Imai, and Tomoyoshi Nozaki.
  • Organizer: VIII European Congress of Protistology (ECOP)
  • Int'l Joint Research
• [Presentation] 赤痢アメーバ原虫のホスファチジルイノシトール代謝酵素のゲノム解析 (2019)
  • Author(s): 津久井久美子, 渡辺菜月, 前濱朝雄, 野崎智義
  • Organizer: 第19回日本蛋白質科学会年会／第71回日本細胞生物学会大会合同年次大会
• [Presentation] Metabolomic analysis uncovers unexpected metabolic pathways in the enteric parasite Entamoeba histolytica (2019)
  • Author(s): Nozaki, T.
  • Organizer: GlycoNov9: 9th Meeting ACETOTRYP/GLYCONOV
  • Int'l Joint Research
• [Presentation] Host modulation by Entamoeba histolytica via secreted lysine and glutamic acid rich protein 2. Eukaryome impact on Intestine homeostasis and mucosal immunology. (2019)
  • Author(s): Nozaki, T. and Das, K.
  • Organizer: Institut Pasteur
  • Int'l Joint Research
• [Presentation] Functional analysis of PI3P effecto candidate SNX in Entamoeba histolytica (2018)
  • Author(s): Natsuki Watanabe, Tomoyoshi Nozaki, Kumiko Nakada-Tsukui
  • Organizer: XIXth International Seminar on Amebiasis
  • Int'l Joint Research
• [Presentation] Discovery of AGC kinase that differentiates trogocytosis from phagocytosis (2018)
  • Author(s): Somlata, Kumiko Nakada-Tsukui, Tomoyoshi Nozaki
  • Organizer: XIXth International Seminar on Amebiasis
  • Int'l Joint Research
• [Presentation] 赤痢アメーバ原虫のホスファチジルイノシトールシグナルと貪食の分子機構 (2018)
  • Author(s): 津久井久美子、渡辺菜月、前濱朝彦、野崎智義
  • Organizer: 26回分子寄生虫学ワークショップ／第16回分子寄生虫学・マラリア研究フォーラム合同大会
• [Presentation] 赤痢アメーバ原虫のホスファチジルイノシトールシグナルと貪食胞成熟の分子機構 (2018)
  • Author(s): 津久井久美子、渡辺菜月、前濱朝彦、野崎智義
  • Organizer: 第91回日本生化学会大会