Malaria parasite invasion of the mosquito salivary gland requires interaction between the Plasmodium TRAP and the Anopheles saglin proteins.
Malaria parasite invasion of the mosquito salivary gland requires interaction between the Plasmodium TRAP and the Anopheles saglin proteins.
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DOI：
10.1371/journal.ppat.1000265
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发表时间：
2009-01
期刊：
影响因子：
6.7
通讯作者：
Jacobs-Lorena, Marcelo
中科院分区：
文献类型：
--
作者：
Ghosh, Anil K.;Devenport, Martin;Jethwaney, Deepa;Kalume, Dario E.;Pandey, Akhilesh;Anderson, Vernon E.;Sultan, Ali A.;Kumar, Nirbhay;Jacobs-Lorena, Marcelo
SM 1是一种由12个氨基酸组成的肽，它与按蚊唾液腺紧密结合，并抑制疟原虫子孢子对其的入侵。通过使用紫外交联实验之间的肽和其唾液腺靶蛋白，我们已经确定了按蚊唾液蛋白，saglin，作为受体的SM 1。此外，通过使用抗SM 1抗体，我们已经确定该肽是疟原虫子孢子血小板反应蛋白相关匿名蛋白（TRAP）的模拟表位。TRAP以高特异性结合saglin。TRAP结合结构域A中的点突变废除结合，并且结合被SM 1肽竞争。重要的是，saglin表达的体内下调导致唾液腺侵袭的强烈抑制。总之，结果表明，saglin/TRAP相互作用是至关重要的唾液腺疟原虫子孢子入侵。疟疾的病原体疟原虫的传播需要蚊子完成一个复杂的生命周期，其中包括侵入唾液腺。这种入侵依赖于寄生虫对蚊子唾液腺表面成分的识别。这项工作表明，唾液腺特异性表面蛋白saglin和寄生虫表面蛋白TRAP之间的相互作用是必不可少的入侵发生。更好地了解寄生虫在蚊子体内发育的机制可能会导致新的方法来干预疾病的传播。
SM1 is a twelve-amino-acid peptide that binds tightly to the Anopheles salivary gland and inhibits its invasion by Plasmodium sporozoites. By use of UV-crosslinking experiments between the peptide and its salivary gland target protein, we have identified the Anopheles salivary protein, saglin, as the receptor for SM1. Furthermore, by use of an anti-SM1 antibody, we have determined that the peptide is a mimotope of the Plasmodium sporozoite Thrombospondin Related Anonymous Protein (TRAP). TRAP binds to saglin with high specificity. Point mutations in TRAP's binding domain A abrogate binding, and binding is competed for by the SM1 peptide. Importantly, in vivo down-regulation of saglin expression results in strong inhibition of salivary gland invasion. Together, the results suggest that saglin/TRAP interaction is crucial for salivary gland invasion by Plasmodium sporozoites. Transmission of Plasmodium, the causative agent of malaria, requires the completion of a complex life cycle in the mosquito, which includes invasion of the salivary glands. This invasion depends on the recognition of mosquito salivary gland surface components by the parasite. This work demonstrates that interaction between the salivary-gland-specific surface protein saglin and the parasite surface protein TRAP is essential for invasion to occur. A better understanding of the mechanisms used by the parasite to develop in the mosquito may lead to novel approaches to intervene with the spread of the disease.
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影响因子：
3.1
作者：
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