Erythrocyte surface glycosylphosphatidyl inositol anchored receptor for the malaria parasite
Erythrocyte surface glycosylphosphatidyl inositol anchored receptor for the malaria parasite
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DOI：
10.1016/j.molbiopara.2004.11.017
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发表时间：
2005-03-01
影响因子：
1.5
通讯作者：
Torii, M
中科院分区：
文献类型：
--
作者：
Rungruang, T;Kaneko, O;Torii, M
寄生液泡的形成是疟原虫成功入侵宿主红细胞的关键步骤。尽管对液泡形成的生物学作用了解甚少，但液泡蛋白被认为在液泡形成中起着重要作用。为了了解寄生虫虫状体蛋白在入侵过程中与红细胞之间的分子相互作用，我们利用啮齿动物疟原虫约氏疟原虫，表征了高分子质量虫状体蛋白（RhopH）复合物与红细胞的结合特异性。RhopH复合物与红细胞的结合是种特异性的，在小鼠中观察到，但在兔或人的红细胞中没有观察到。用胰蛋白酶或凝乳胰蛋白酶治疗红细胞后，结合被废除。由于宿主细胞富含胆固醇的膜结构域被招募到新生寄生物液泡中，我们评估了RhopH复合物与富含胆固醇的膜结构域相关的糖基磷脂酰肌醇（GPI）锚定蛋白结合的可能作用。在含有gpi缺陷红细胞的嵌合小鼠中，检测不到RhopH复合物与gpi缺陷小鼠红细胞的结合，这表明gpi锚定蛋白参与了PyRhopH复合物的结合。此外，在体内观察到gpi缺陷红细胞的R - yoelii寄生虫感染显著减少，可能是由于低效入侵。我们得出结论，PyRhopH复合物的主要红细胞受体是一种通过gpi锚点附着在红细胞表面的蛋白质，gpi缺乏的红细胞对P. yoelii的侵袭具有抗性。(C) 2004 Elsevier B.V.版权所有
Parasitophorous vacuole formation is a critical step for the successful invasion of host erythrocytes by the 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. RhopH complex binding to erythrocytes was species-specific, observed with mouse but not rabbit or human erythrocytes. Binding is abolished following treatment of erythrocytes with trypsin or chymotrypsin. Because host cell cholesterol-rich membrane domains are recruited into the nascent parasitophorous vacuole, we evaluated a possible role of RhopH complex binding to the cholesterol-rich membrane domain-associated glycosylphosphatidyl inositol (GPI)-anchored protein. Using chimeric mice harboring GPI-deficient erythrocytes, RhopH complex binding to GPI-deficient mouse erythrocytes was undetectable, indicating involvement of GPI-anchored protein in PyRhopH complex binding. Furthermore, a significant reduction of R yoelii parasite infection of GPI-deficient erythrocytes was observed in vivo, probably due to inefficient invasion. We conclude that the major erythrocyte receptor for PyRhopH complex is a protein attached to the erythrocyte surface via GPI-anchor and that GPI-deficient erythrocytes are resistant to P. yoelii invasion. (C) 2004 Elsevier B.V. All rights reserved.