Role of KERP2 as a potential regulator in Entamoeba histolytica and the human host

2023 Fiscal Year Final Research Report

• Project/Area Number: 21K19372
• Research Category: Grant-in-Aid for Challenging Research (Exploratory)
• Allocation Type: Multi-year Fund
• Review Section: Medium-sized Section 49:Pathology, infection/immunology, and related fields
• 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): 津久井 久美子 国立感染症研究所, 寄生動物部, 主任研究官 (00420092) ; サントス ハルベルト・ヒメネス 東京大学, 大学院医学系研究科(医学部), 助教 (90793779)
• Project Period (FY): 2021-07-09 – 2024-03-31
• Keywords: 原虫 / 宿主制御 / 分泌 / 核移行

Outline of Final Research Achievements

Entamoeba histolytica is a parasitic protist that heavily depends on parasite-host interactions. A comprehensive understanding of the proteins that mediate parasite-host interactions is essential for decoding this parasite's pathogenicity. A recently identified lysine and glutamic acid-rich proteins (KERPs) are known to interact with the brush border of human intestinal cells. In this study we investigated functional role of KERP2, by employing strategies such as epitope-tagging, gene silencing, and multi-omics. Our data suggest that KERP2 functions as a gene repressor, controlling ribosome biogenesis in the parasite. We also note that KERP2 exhibits translocation from the parasite to the enterocytes. We identified a panel of proteins that bound to KERP2 in Caco-2 cells. Furthermore, we also found that a set of genes from several pathways were regulated by KERP2 in humans.

Free Research Field

寄生虫学、感染症学、病原学

Academic Significance and Societal Importance of the Research Achievements

以上の赤痢アメーバのKERP2に関する研究成果は、腸管内寄生原虫が、液性因子を放出して、宿主の細胞・組織に作用し、その機能や遺伝子発現をどのように修飾・制御するかを示す世界で初めての画期的な成果を提供したと言える。