Department of Biological Sciences and Institute for Global Health, Vanderbilt University, Nashville, Tennessee 37235, USA.
J Biol Chem. 2011 Nov 25;286(47):40824-34. doi: 10.1074/jbc.M111.280552. Epub 2011 Sep 29.
Mosquitoes transmit Plasmodium and certain arboviruses during blood feeding, when they are injected along with saliva. Mosquito saliva interferes with the host's hemostasis and inflammation response and influences the transmission success of some pathogens. One family of mosquito salivary gland proteins, named SGS, is composed of large bacterial-type proteins that in Aedes aegypti were implicated as receptors for Plasmodium on the basal salivary gland surface. Here, we characterize the biology of two SGSs in the malaria mosquito, Anopheles gambiae, and demonstrate their involvement in blood feeding. Western blots and RT-PCR showed that Sgs4 and Sgs5 are produced exclusively in female salivary glands, that expression increases with age and after blood feeding, and that protein levels fluctuate in a circadian manner. Immunohistochemistry showed that SGSs are present in the acinar cells of the distal lateral lobes and in the salivary ducts of the proximal lobes. SDS-PAGE, Western blots, bite blots, and immunization via mosquito bites showed that SGSs are highly immunogenic and form major components of mosquito saliva. Last, Western and bioinformatic analyses suggest that SGSs are secreted via a non-classical pathway that involves cleavage into a 300-kDa soluble fragment and a smaller membrane-bound fragment. Combined, these data strongly suggest that SGSs play an important role in blood feeding. Together with their role in malaria transmission, we propose that SGSs could be used as markers of human exposure to mosquito bites and in the development of disease control strategies.
蚊子在吸血时会传播疟原虫和某些虫媒病毒，此时它们会随着唾液一起注入人体。蚊子的唾液会干扰宿主的止血和炎症反应，并影响某些病原体的传播成功率。蚊子唾液腺蛋白的一个家族，称为 SGS，由大型细菌型蛋白组成，在埃及伊蚊中，这些蛋白被认为是基唾液腺表面上疟原虫的受体。在这里，我们描述了疟蚊 Anopheles gambiae 中两种 SGS 的生物学特性，并证明了它们在吸血中的作用。Western blot 和 RT-PCR 显示，Sgs4 和 Sgs5 仅在雌性唾液腺中产生，其表达随年龄和吸血而增加，并且蛋白水平呈昼夜节律波动。免疫组织化学显示，SGS 存在于远端侧叶的腺泡细胞和近端叶的唾液道中。SDS-PAGE、Western blot、咬斑和通过蚊子叮咬进行免疫接种表明，SGS 高度免疫原性，是蚊子唾液的主要成分。最后，Western blot 和生物信息学分析表明，SGS 通过一种非经典途径分泌，涉及 300 kDa 可溶性片段和较小的膜结合片段的切割。综合这些数据强烈表明 SGS 在吸血中起重要作用。结合它们在疟疾传播中的作用，我们提出 SGS 可以用作人类暴露于蚊子叮咬的标志物，并可用于开发疾病控制策略。
