Signaling mechanism of the apical organelle discharge by malaria parasites during erythrocyte invasion

2022 Fiscal Year Final Research Report

• Project/Area Number: 19H03461
• 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: Nagasaki University
• Principal Investigator: KANEKO Osamu 長崎大学, 熱帯医学研究所, 教授 (50325370)
• Co-Investigator(Kenkyū-buntansha): 矢幡 一英 愛媛大学, プロテオサイエンスセンター, 准教授 (40467965) ; 石崎 隆弘 長崎大学, 熱帯医学研究所, 助教 (40880810) ; 麻田 正仁 長崎大学, 熱帯医学研究所, 助教 (40587028)
• Project Period (FY): 2019-04-01 – 2022-03-31
• Keywords: マラリア / 病原性原虫 / 赤血球 / 細胞侵入 / シグナル伝達

Outline of Final Research Achievements

The main objective of the study was to identify the signaling molecules involved in molecular secretion from the microorganelles of the Plasmodium parasites for erythrocyte invasion. We found that two pseudokinases contribute not only to erythrocyte invasion but also to the exflagellar center formation by the male gametes. We also found that the two diacylglycerol kinases are not essential when each is destroyed, but parasites' viability was severely impaired when destroyed simultaneously. We found that a molecule called APH, which is located downstream of signaling through diacylglycerol kinase, was involved in the secretion of molecules called AMA1 and MTRAP. In the process of video analysis, we also found that merozoites have gliding motility.

Free Research Field

寄生虫学

Academic Significance and Societal Importance of the Research Achievements

マラリア原虫の赤血球侵入に当たり、細胞内分泌小器官から分泌される種々のワクチン候補抗原の分泌トリガーとそれらをつなぐシグナル伝達に関わる分子を明らかにすることにより、生物学的には、理解が進んでいない赤血球侵入期のシグナル伝達経路の全体像に迫ることができ、明らかとなる分子機能の深い理解に立脚した新たなワクチン構想や創薬が可能となる。特に本研究で見出したメロゾイトの滑走運動は、新たな創薬標的機序となることも期待できる。