A multidomain adhesion protein family expressed in Plasmodium falciparum is essential for transmission to the mosquito
A multidomain adhesion protein family expressed in Plasmodium falciparum is essential for transmission to the mosquito
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DOI：
10.1084/jem.20031274
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发表时间：
2004-06-07
影响因子：
15.3
通讯作者：
Templeton, TJ
中科院分区：
文献类型：
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作者：
Pradel, G;Hayton, K;Templeton, TJ
最近对几个顶端复合体基因组的测序为表征寄生虫生命周期所必需的新抗原提供了机会，这可能会导致新的诊断和治疗市场的发展。在这里，我们筛选了恶性疟原虫基因组序列中编码细胞外多结构域假定黏附蛋白的基因。其中三个已鉴定的基因，命名为PfCCp1、PfCCp2和PfCCp3，具有多个黏附模块，包括在另外两个疟原虫基因中也发现的共同的蛙凝血因子C结构域。在微小隐孢子虫基因组序列中发现了同源基因，表明其具有进化保守功能。转录和蛋白表达分析显示PfCCp1、PfCCp2和PfCCp3在有性阶段特异表达，细胞定位研究表明在成熟配子细胞中存在质膜相关表达。在配子发生过程中，PfCCps被释放并定位于新出现的微配子和大配子的周围复合体。受精卵形成后，PfCCp的表达显著降低。为了开始解决PfCCp的功能，PfCCp2和PfCCp3基因座被同源重组打乱，导致能够形成卵囊子孢子的寄生虫，但阻止了唾液腺的过渡。我们的结果描述了在有性期表达的一个保守的顶端复合体蛋白家族的成员，该蛋白可能代表传播阻断疫苗的候选亚单位。
The recent sequencing of several apicomplexan genomes has provided the opportunity to characterize novel antigens essential for the parasite life cycle that might lead to the development of new diagnostic and therapeutic markets. Here we have screened the Plasmodium falciparum genome sequence for genes encoding extracellular multidomain putative adhesive proteins. Three of these identified genes, named PfCCp1, PfCCp2, and PfCCp3, have multiple adhesive modules including a common Limulus coagulation factor C domain also found in two additional Plasmodium genes. Orthologues were identified in the Cryptosporidium parvum genome sequence, indicating an evolutionary conserved function. Transcript and protein expression analysis shows sexual stage-specific expression of PfCCp1, PfCCp2, and PfCCp3, and cellular localization studies revealed plasma membrane-associated expression in mature gametocytes. During gametogenesis, PfCCps are released and localize surrounding complexes of newly emerged microgametes and macrogametes. PfCCp expression markedly decreased after formation of zygotes. To begin to address PfCCp function, the PfCCp2 and PfCCp3 gene loci were disrupted by homologous recombination, resulting in parasites capable of forming oocyst sporozoites but blocked in the salivary gland transition. Our results describe members of a conserved apicomplexan protein family expressed in sexual stage Plasmodium parasites that may represent candidates for subunits of a transmission-blocking vaccine.