Plasmodium carbohydrate receptors in Anopheles gambiae

冈比亚按蚊的疟原虫碳水化合物受体

• 批准号: 7269916
• 负责人: Rhoel David Ramos Dinglasan
• 金额: $ 5.04万
• 依托单位: JOHNS HOPKINS UNIVERSITY
• 依托单位国家: 美国
• 财政年份: 2006
• 资助国家: 美国
• 起止时间: 2006-07-01 至 2009-06-30
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/7269916
• 关键词: Adult; Anopheles Genus; Anopheles gambiae; Antibodies; Biochemical; Biology; Blood; Brush Border; Carbohydrates; Cell Line; Culicidae; Cultured Cells; Development; Disruption; Drug or chemical Tissue Distribution; Enzymes; Family; Fluorescence Microscopy; Gene Silencing; Genes; Genome; Glycoconjugates; Glycoproteins; Glycosyltransferase Gene; Goals; Golgi Apparatus; In Vitro; Malaria; Measures; Mediating; Midgut; Molecular; Mucins; Numbers; Oocysts; Parasites; Plasmodium; Polysaccharides; Process; Proteins; RNA Interference; Range; Recombinant Proteins; Research; Reverse Transcriptase Polymerase Chain Reaction; Role; Structure; Substrate Specificity; Testing; Transferase; Ursidae Family; Vertebral column; carbohydrate binding protein; carbohydrate receptor; glycosylation; glycosyltransferase; in vivo; polypeptide; positional cloning

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.

描述（由申请方提供）：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状缘上，而且还完全阻断寄生虫发育。由于可以携带这些聚糖的全部多肽骨架的身份是未知的，因此特异性蛋白质靶向是不可行的。然而，已知向多肽（如粘蛋白和其他肠糖蛋白）添加特定聚糖是由肠高尔基体中确定的常驻转移酶家族调节的。我们推测，动合子附着可以通过中断中肠腔糖蛋白的糖基化来减少或完全抑制。为了验证这一假设，我们设想了一个两步的过程：1）分子鉴定和生物化学表征的蚊子中肠酶参与中肠刷状缘糖蛋白的糖基化，和2）使用反向遗传学（RNAi基因沉默），以评估选定的中肠特异性糖基化酶的功能作用疟原虫感染。这一系列实验将通过对蚊子中肠生物学的基本糖生物学分析开辟新的研究途径。