Specific traffic system mediated by lipid in Entamoeba histolytica

2018 Fiscal Year Final Research Report

• Project/Area Number: 16K08768
• Research Category: Grant-in-Aid for Scientific Research (C)
• Allocation Type: Multi-year Fund
• Section: 一般
• Research Field: Parasitology (including sanitary zoology)
• Research Institution: National Institute of Infectious Diseases
• Principal Investigator: Saito-NAKANO Yumiko (斉藤由美子) 国立感染症研究所, 寄生動物部, 主任研究官 (30321764)
• Research Collaborator: Nakasone Eiko ; Hanadate Yuki ; Kawano Tetsuro
• Project Period (FY): 2016-04-01 – 2019-03-31
• Keywords: 赤痢アメーバ / メンブラントラフィック / 小胞体 / Rab GTPase

Outline of Final Research Achievements

In enteric protozoan parasite Entamoeba histolytica, EhRab8A GTPase is localized to the ER and needed for the correct transport of surface molecules, which might be needed for the cellular adhesion. In this work, I identified one of the binding protein of EhRab8A, homologue of Cdc50. In mammal, Cdc50 codes a non-catalytic subunit of lipid flippase P4-ATPase and localized to the plasma membrane. EhCdc50-overexpressing transformant amoeba showed that the accumulation of EhCdc50 to the amoebic ER and showed miltefosine resistance, that is broad anti-parasitic phosphocholine analogue. As a second EhRab8A dependent cargo protein, novel molecule EHI_159620 was identified by the biotinylation of constitutively-active EhRab8A expressing cells. Identification of these novel binding proteins of EhRab8A may reveal diverse traffic system in protozoa.

Free Research Field

分子寄生虫学

Academic Significance and Societal Importance of the Research Achievements

一般的な分泌タンパク質は、小胞体でCOPII小胞に包まれ、ゴルジ体を経て細胞表面に輸送される。COPII小胞に包まれるには、Sar1 GTPaseの機能が必要である。本研究では嫌気性寄生原虫の赤痢アメーバでは、RabファミリーのGTPaseが小胞体に局在し、小胞体から細胞表面への輸送を担う経路があることを発見した。この現象は、原虫におけるunconventional secretion の存在を示し、多様な輸送機構の理解に貢献する。