| Project/Area Number |
16390124
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| Research Category |
Grant-in-Aid for Scientific Research (B)
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| Allocation Type | Single-year Grants |
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| Section | 一般 |
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| Research Field |
Parasitology (including Sanitary zoology)
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| Research Institution | Mie University |
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Principal Investigator |
YUDA Masao Mie University, Faculty of Medicine, Assistant Professor, 大学院・医学系研究科, 助教授 (90293779)
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| Project Period (FY) |
2004 – 2005
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| Project Status |
Completed (Fiscal Year 2005)
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| Budget Amount *help |
¥14,900,000 (Direct Cost: ¥14,900,000)
Fiscal Year 2005: ¥7,200,000 (Direct Cost: ¥7,200,000)
Fiscal Year 2004: ¥7,700,000 (Direct Cost: ¥7,700,000)
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| Keywords | Malaria / ookinet / mosquito / membrane rupture / ハマダラ蚊 / 感染機構 / 中腸 / パーホリン様分子 / パーホリン |
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| Research Abstract |
After ingestion of infected blood by a mosquito, malarial parasites are fertilized in the mosquito midgut and develop into motile ookinetes. These ookinetes invade epithelial cells by rupturing the cell membrane and migrate through the cytoplasm toward the basal lamina, on which they develop to oocysts. In this study we found that a microneme protein with a membrane-attack complex and perforin (MACPF) -related domain, which we name membrane-attack ookinete protein (MAOP), is produced in the ookinete stage and plays an essential role in midgut invasion by the ookinete. Ookinetes with the MAOP gene disrupted completely lost infectivity to the midgut. After ingestion of blood infected with the disrupted parasite, the midgut epithelium remained intact, making a clear contrast with the damaged midgut epithelium invaded by wild-type ookinetes. Electron microscopic analysis showed that the disruptant ookinetes migrate to the gut epithelium and attach to the cell surface at the apical tip, but are unable to enter the cytoplasm by rupturing the cell membrane. These results indicate that the MAOP molecule acts on the plasma membrane of the host-cell-like mammalian MACPF family proteins that create pores in the membrane of target cells. Another previously identified MACPF-related molecule (SPECT2) is produced in the liver-infective sporozoite and has a crucial role in traversing the liver sinusoidal cell boundary. The present finding, thus, suggests that conserved mechanisms for membrane rupture involving MACPF-related proteins are used in different host invasive stages of the malarial parasite, playing a key role in breaching biological barriers of host organs.
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