Functional analysis of lipid transfer proteins from Entamoeba histolytica

2023 Fiscal Year Final Research Report

• Project/Area Number: 21H02723
• 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): 渡邊 菜月 東京大学, 大学院医学系研究科(医学部), 客員研究員 (00883323)
• Project Period (FY): 2021-04-01 – 2024-03-31
• Keywords: 脂質 / 輸送 / 感染症 / 寄生虫 / 病原機構

Outline of Final Research Achievements

Phospholipids, their biosynthesis, and functional implications in the nucleus have been recently unraveled from eukaryotes. In the present study, we have identified for the first time a lipid transfer protein (LTP) from a protozoan parasite E. histolytica (EhLTP15) that is involved in nuclear-cytoplasmic lipid transport and regulation of nuclear lipid metabolism and homeostasis. EhLTP15 translocated from the nucleus to the cytoplasm under nutrient deprived conditions. EhLTP15 was also involved in exocytosis of pinocytosed fluid phase maker and secretion of lysosomal enzymes, cysteine proteases, which are implicated for virulence and tissue invasion of this enteric pathogen. EhLTP15 was also involved in the defense against oxidative stress. Furthermore, EhLTP15 was necessary to maintain the levels of nuclear phosphoinositides. This study has provided a link between non-vesicular lipid transport and nuclear lipid metabolism for the first time in any unicellular eukaryotes.

Free Research Field

寄生虫学、感染症学、病原学

Academic Significance and Societal Importance of the Research Achievements

本研究成果はLTPsの核内のリン脂質の代謝と病原性への関与を原虫で初めて示した点で極めて新規性が高く、更に、真核生物におけるLTPsの多様性と機能の進化と普遍性の理解の助けとなった。同時に、本研究成果は赤痢アメーバの治療・予防への応用を可能とする基盤的な成果となった。本研究成果は他の寄生虫症やヒトの疾患の病態や治療法の理解に役立つ情報を提供したということができる。