Plasmodium carbohydrate receptors in Anopheles gambiae

描述(申请人提供)：碳水化合物和碳水化合物结合蛋白不仅抑制寄生虫附着在中肠刷子边缘，而且完全阻止寄生虫的发展。由于能够承载这些糖链的全系列多肽骨架的身份尚不清楚，因此特定的蛋白质靶向是不可行的。然而，已知的是，特定的多糖添加到多肽，如粘蛋白和其他肠道糖蛋白，是由肠道高尔基体中特定的常驻转移酶家族调节的。我们假设，通过阻断中肠腔糖蛋白的糖基化可以减少或完全抑制运动附着。为了验证这一假说，我们设想了一个两步过程：1)参与中肠刷状缘糖蛋白糖基化的蚊子中肠酶的分子鉴定和生化特征，以及2)使用反向遗传学(RNAi基因沉默)来评估选定的中肠特异性糖基化酶在疟原虫感染中的功能作用。这一系列实验将通过对蚊子中肠生物学进行基本的糖生物学分析，开辟新的研究途径。

DESCRIPTION (provided by applicant): Carbohydrates and carbohydrate-binding proteins not only inhibit parasite attachment to the midgut brush border but completely block parasite development as well. Since the identity of the full range of polypeptide backbones that can bear these glycans is unknown, specific protein targeting is unfeasible. However, it is known that addition of specific glycans to polypeptides, such as mucins and other gut glycoproteins are regulated by a defined family of resident transferases in the gut Golgi. We hypothesize that ookinete attachment can be reduced or completely inhibited by interrupting glycosylation of midgut lumenal glycoproteins. To test this hypothesis, we envision a two-step process: 1) molecular identification and biochemical characterization of mosquito midgut enzymes involved in the glycosylation of midgut brush border glycoproteins, and 2) the use of reverse genetics (RNAi gene silencing) to assess the functional role of selected midgut-specific glycosylation enzymes on Plasmodium infection. This line of experimentation will open up new avenues of research through the basic, glycobiological analysis of the mosquito midgut biology.