Genetic ablation of a Maurer's cleft protein prevents assembly of the Plasmodium falciparum virulence complex
Genetic ablation of a Maurer's cleft protein prevents assembly of the Plasmodium falciparum virulence complex
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DOI：
10.1111/j.1365-2958.2011.07740.x
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发表时间：
2011-08-01
影响因子：
3.6
通讯作者：
Tilley, Leann
中科院分区：
文献类型：
--
作者：
Dixon, Matthew W. A.;Kenny, Shannon;Tilley, Leann
疟原虫恶性疟原虫在红细胞膜下方组装旋钮结构，帮助呈现主要毒力蛋白恶性疟原虫红细胞膜蛋白 1 (PfEMP1)。红细胞细胞质中建立了称为毛雷氏裂的膜结构，其功能是在通往红细胞膜的途中对蛋白质进行分选，包括旋钮相关富含组氨酸蛋白 (KAHRP) 和 PfEMP1。我们已经生成了突变体，其中毛雷氏裂蛋白、环输出蛋白-1 (REX1) 被截短或删除。去除 REX1 的 C 端结构域会损害 Maurer 裂结构和 PfEMP1 介导的细胞粘附，但允许 PfEMP1 部分转运至红细胞表面。删除 REX1 的卷曲线圈区域会消除 PfEMP1 的表面显示，将 PfEMP1 捕获在 Maurer 裂口处。突变体与 REX1 的互补部分恢复了 PfEMP1 介导的与内皮细胞配体 CD36 的结合。卷曲螺旋区域的缺失或 REX1 的完全缺失与编码 KAHRP 和其他蛋白质的 2 号染色体亚端粒区域的丢失密切相关。 REX1 缺失寄生虫中表达的 KAHRP-绿色荧光蛋白 (GFP) 融合物显示运输缺陷。因此，功能性 REX1 的丧失直接或间接地消除了恶性疟原虫毒力复合物在宿主红细胞表面的组装。
The malaria parasite Plasmodium falciparum assembles knob structures underneath the erythrocyte membrane that help present the major virulence protein, P. falciparum erythrocyte membrane protein-1 (PfEMP1). Membranous structures called Maurer's clefts are established in the erythrocyte cytoplasm and function as sorting compartments for proteins en route to the RBC membrane, including the knob-associated histidine-rich protein (KAHRP), and PfEMP1. We have generated mutants in which the Maurer's cleft protein, the ring exported protein-1 (REX1) is truncated or deleted. Removal of the C-terminal domain of REX1 compromises Maurer's cleft architecture and PfEMP1-mediated cytoadherance but permits some trafficking of PfEMP1 to the erythrocyte surface. Deletion of the coiled-coil region of REX1 ablates PfEMP1 surface display, trapping PfEMP1 at the Maurer's clefts. Complementation of mutants with REX1 partly restores PfEMP1-mediated binding to the endothelial cell ligand, CD36. Deletion of the coiled-coil region or complete deletion of REX1 is tightly associated with the loss of a subtelomeric region of chromosome 2, encoding KAHRP and other proteins. A KAHRP-green fluorescent protein (GFP) fusion expressed in the REX1-deletion parasites shows defective trafficking. Thus, loss of functional REX1 directly or indirectly ablates the assembly of the P. falciparum virulence complex at the surface of host erythrocytes.