Identification of the erythrocyte receptor for Plasmodium yoelii RhopH complex

约氏疟原虫 RhopH 复合物红细胞受体的鉴定

• 批准号: 16017272
• 负责人: TORII Motomi
• 金额: $ 9.6万
• 依托单位: Ehime University
• 依托单位国家: 日本
• 项目类别: Grant-in-Aid for Scientific Research on Priority Areas
• 财政年份: 2004
• 资助国家: 日本
• 起止时间: 2004 至 2005
• 项目状态: 已结题
• 来源: https://kaken.nii.ac.jp/en/grant/KAKENHI-PROJECT-16017272/
• 关键词: infectious disease; malaria; Plasmodium; マラリア原虫; 赤血球結合蛋白質; レセプター; GPIアンカー

Parasitophorous vacuole formation is a critical step for the successful invasion of host erythrocytes by malaria parasite. Rhoptry proteins are believed to have essential roles in vacuole formation, although their biological roles are poorly understood. To understand the molecular interactions between parasite rhoptry proteins and the erythrocyte during invasion, we have characterized the binding specificity of the high molecular mass rhoptry protein (RhopH) complex to erythrocytes using the rodent malaria parasite, Plasmodium yoelii and proposed that the major erythrocyte receptor for PyRhopH complex is a protein attached to the erythrocyte surface via GPI-anchor.To further characterize and identify the unknown receptor protein, we employed forward genetic analysis using consomic mouse strains derived from C57BL/6J (B6) and MSM/Ms strains based on the difference in the PyRhopH complex binding to the erythrocytes from these mice (erythrocytes from B6 exhibited higher binding than MSM/Ms). These consomic strains have B6 genetic background and a particular chromosome or chromosomal region is replaced with the one from MSM/Ms. A panel of consomic strains available were examined and the binding among consomic strains were found to be not clearly differentiate to B6 type or MSM/Ms type, indicating that multiple factors were involved in the observed binding. However B6-11^<MSM/Ms>, which harbored chromosome 11 derived from MSM/Ms, showed a prominent low binding, even lower than MSM/Ms, thus we considered that the receptor protein potentially located on chromosome 11. Based on this assumption, we are in a process to narrow the candidate region on the chromosome 11 by further linkage analysis between B6 and B6-11^<MSM/Ms>. The GPI-anchored protein on the candidate region would be characterized as a prime candidate for the PyRhopH complex receptor.

疟原虫空泡的形成是疟原虫成功侵入宿主红细胞的关键步骤。棒状体蛋白被认为在液泡形成中具有重要作用，尽管它们的生物学作用知之甚少。为了了解寄生虫棒状体蛋白和红细胞在入侵过程中的分子相互作用，我们已经使用啮齿类疟原虫表征了高分子量棒状体蛋白（RhopH）复合物与红细胞的结合特异性，约氏疟原虫，并提出PyRhopH复合物的主要红细胞受体是一种通过GPI附着在红细胞表面的蛋白质。锚。为了进一步表征和鉴定未知受体蛋白，我们使用来自C57 BL/6 J（B6）和MSM/Ms品系的同源小鼠品系，基于PyRhopH复合物与这些小鼠的红细胞结合的差异进行正向遗传分析（来自B6的红细胞表现出比MSM/Ms更高的结合）。这些consomic菌株具有B6遗传背景，并且特定的染色体或染色体区域被来自MSM/Ms的染色体或染色体区域所取代。检查了一组可用的consomic菌株，发现consomic菌株之间的结合不能清楚地区分为B6型或MSM/Ms型，表明观察到的结合涉及多种因素。然而，B6-11^<MSM/Ms>，其具有来自MSM/Ms的11号染色体，显示出显著的低结合，甚至低于MSM/Ms，因此我们认为受体蛋白可能位于11号染色体上。基于这一假设，我们正在通过进一步的B6和B6-11^<MSM/Ms>之间的连锁分析来缩小11号染色体上的候选区域。候选区域上的GPI锚定蛋白将被表征为PyRhopH复合物受体的主要候选物。

项目成果

2-Cys peroxiredoxin TPx-1 is involved in gametocyte development in Plasmodium berghei

• DOI: 10.1016/j.molbiopara.2006.02.018
• 发表时间: 2006-07-01
• 期刊: MOLECULAR AND BIOCHEMICAL PARASITOLOGY
• 影响因子: 1.5
• 作者: Yano, Kazuhiko;Komaki-Yasuda, Kanako;Kawazu, Shin-ichiro
• 通讯作者: Kawazu, Shin-ichiro

Apical expression of three RhopH1/Clag proteins as components of th Plasmodium falciparum RhopH complex

作为恶性疟原虫 RhopH 复合物成分的三种 RhopH1/Clag 蛋白的顶端表达

• 发表时间: 2005
• 期刊: Molecular and Biochemical Parasitology 143
• 作者: Kaneko 0;Yim-Lim BYS;Iriko H;Ling IT;Otsuki H;Grainger M;Tsuboi T;Adams JH;Mattei D;Holder AA;Torii M.;Kaneko O et al.
• 通讯作者: Kaneko O et al.

Nasal immunization with a malaria transmission-blocking vaccine candidate Pfs25 induces complete protective immunity in mice against field-isolated Plasmodium falciparum

使用阻断疟疾传播的候选疫苗 Pfs25 进行鼻免疫可诱导小鼠针对现场隔离的恶性疟原虫产生完全保护性免疫力

• 发表时间: 2005
• 期刊: Infection and Immunity 73
• 作者: Arakawa T;et. al.
• 通讯作者: et. al.

Apical expression of three RhopHl/Clag proteins as components of the Plasmodium falcioarum RhopH complex.

作为镰状疟原虫 RhopH 复合物成分的三种 RhopH1/Clag 蛋白的顶端表达。

• 发表时间: 2005
• 期刊: Mol Biochem Parasitol 143(1)
• 作者: Kaneko 0;Yim-Lim BYS;Iriko H;Ling IT;Otsuki H;Grainger M;Tsuboi T;Adams JH;Mattei D;Holder AA;Torii M.
• 通讯作者: Torii M.

Antibodies against MAEBL ligand domains M1 and M2 inhibit sporozoite development in vitro

• DOI: 10.1128/iai.72.6.3604-3608.2004
• 发表时间: 2004-06-01
• 期刊: INFECTION AND IMMUNITY
• 影响因子: 3.1
• 作者: Preiser, P;Rénia, L;Adams, JH
• 通讯作者: Adams, JH