Dessens Johannes T, Sidén-Kiamos Inga, Mendoza Jacqui, Mahairaki Vassiliki, Khater Emad, Vlachou Dina, Xu Xiao-Jin, Kafatos Fotis C, Louis Christos, Dimopoulos George, Sinden Robert E
Department of Biological Sciences, Sir Alexander Fleming Building, Imperial College London, South Kensington Campus, SW7 2AZ, UK.
Mol Microbiol. 2003 Jul;49(2):319-29. doi: 10.1046/j.1365-2958.2003.03566.x.
An essential, but poorly understood part of malaria transmission by mosquitoes is the development of the ookinetes into the sporozoite-producing oocysts on the mosquito midgut wall. For successful oocyst formation newly formed ookinetes in the midgut lumen must enter, traverse, and exit the midgut epithelium to reach the midgut basal lamina, processes collectively known as midgut invasion. After invasion ookinete-to-oocyst transition must occur, a process believed to require ookinete interactions with basal lamina components. Here, we report on a novel extracellular malaria protein expressed in ookinetes and young oocysts, named secreted ookinete adhesive protein (SOAP). The SOAP gene is highly conserved amongst Plasmodium species and appears to be unique to this genus. It encodes a predicted secreted and soluble protein with a modular structure composed of two unique cysteine-rich domains. Using the rodent malaria parasite Plasmodium berghei we show that SOAP is targeted to the micronemes and forms high molecular mass complexes via disulphide bonds. Moreover, SOAP interacts strongly with mosquito laminin in yeast-two-hybrid assays. Targeted disruption of the SOAP gene gives rise to ookinetes that are markedly impaired in their ability to invade the mosquito midgut and form oocysts. These results identify SOAP as a key molecule for ookinete-to-oocyst differentiation in mosquitoes.
疟原虫通过蚊子传播这一过程中，有一个重要但却鲜为人知的环节，即动合子在蚊子中肠壁上发育成产生子孢子的卵囊。为了成功形成卵囊，中肠腔中新形成的动合子必须进入、穿过并离开中肠上皮细胞，到达中肠基膜，这些过程统称为中肠入侵。入侵后，动合子向卵囊的转变必须发生，这一过程被认为需要动合子与基膜成分相互作用。在此，我们报道了一种在动合子和年轻卵囊中表达的新型细胞外疟原虫蛋白，命名为分泌型动合子黏附蛋白（SOAP）。SOAP基因在疟原虫物种中高度保守，且似乎是该属所特有的。它编码一种预测的分泌型可溶性蛋白，其模块化结构由两个独特的富含半胱氨酸的结构域组成。利用啮齿动物疟原虫伯氏疟原虫，我们发现SOAP定位于微线体，并通过二硫键形成高分子量复合物。此外，在酵母双杂交试验中，SOAP与蚊子层粘连蛋白强烈相互作用。对SOAP基因进行靶向破坏会导致动合子入侵蚊子中肠并形成卵囊的能力显著受损。这些结果表明SOAP是蚊子中动合子向卵囊分化的关键分子。
