Novel secretion mechanisms from ER independent of signal peptide in protozoan parasites

2022 Fiscal Year Final Research Report

• Project/Area Number: 19K07531
• Research Category: Grant-in-Aid for Scientific Research (C)
• Allocation Type: Multi-year Fund
• Section: 一般
• Review Section: Basic Section 49040:Parasitology-related
• 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)
• Project Period (FY): 2019-04-01 – 2023-03-31
• Keywords: 赤痢アメーバ / マラリア原虫 / Rab GTPase / メンブレントラフィック

Outline of Final Research Achievements

The N-terminus signal peptide of secreted proteins is required for the protein to be transported out of the endoplasmic reticulum. However, several secreted proteins without a signal peptide have been reported in protozoa and host cells. In this study, I showed that EhTolA is transported to the cell surface by the endoplasmic reticulum-localized Rab8A GTPase in Entamoeba histolytica. N-terminal myristylation modification of EhTolA was necessary for transport to the amebic cell surface. In addition, myristoylated PfRab5b GTPase, which is localized to the ER, is involved in the transport of myristoylated substrate, AK2, to the parasitophorous vacuolar membrane in Plasmodium falciparum. The regulatory factors involved in the regulation of PfRab5b were also analyzed.

Free Research Field

細胞生物学

Academic Significance and Societal Importance of the Research Achievements

寄生性原虫は宿主表面の抗原を認識・接着した後に細胞侵入を開始するため、原虫の細胞表面への表面抗原の輸送機構の解明は重要である。本申請課題で解析を行った赤痢アメーバとマラリア原虫は共に国内外で感染者が多く、感染防御の機構解明が必要である。本研究結果により赤痢アメーバとマラリア原虫は、共に特殊な細胞内輸送系を獲得していることが明らかになった。