Plasmodium carbohydrate receptors in Anopheles gambiae

描述（由申请人提供）：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边缘，而且完全阻断寄生虫的发育。由于能够承受这些聚糖的全部多肽骨架的身份是未知的，因此特异性的蛋白质靶向是不可行的。然而，已知的是，特定的聚糖添加到多肽，如粘蛋白和其他肠道糖蛋白是由肠道高尔基体中一个确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卵母细胞的附着。为了验证这一假设，我们设想了一个两步的过程：1)参与蚊子中肠刷状边缘糖蛋白糖基化的酶的分子鉴定和生化表征；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。这一系列的实验将通过对蚊子中肠生物学的基础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.