CD46 as a Signaling Intermediate in N. Gonorrhoeae Infection

CD46 作为淋病奈瑟菌感染中的信号传导中间体

• 批准号: 8282798
• 负责人: MAGDALENE Y SO
• 金额: $ 37.5万
• 依托单位: UNIVERSITY OF ARIZONA
• 依托单位国家: 美国
• 财政年份: 2010
• 资助国家: 美国
• 起止时间: 2010-06-01 至 2014-05-31
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/8282798
• 关键词: Adenoviruses; Affect; Bacteria; Biological; CD46 Antigen; Cells; Cleaved cell; Complex; Cytoplasmic Tail; Development; Disease; Epithelial Cells; Event; Goals; Herpesviridae; Human; Immune system; Infection; Knowledge; Link; Matrix Metalloproteinases; Membrane; Membrane Proteins; Modeling; Molecular; Nature; Neisseria; Neisseria gonorrhoeae; Neisseria meningitidis; Outcome; Peptide Hydrolases; Phenotype; Phosphorylation; Pilum; Process; Property; Protein Isoforms; Proteins; Proteolytic Processing; Receptor Signaling; Relative (related person); Role; Signal Transduction; Streptococcus pyogenes; Testing; Virus; microbial; presenilin; receptor; secretase; trafficking

ABSTRACT CD46 is a human-specific membrane protein with numerous signaling and receptor properties. Despite the multifunctional nature of this protein, little is known about the molecular mechanisms underlying its biological phenotypes. Several viruses and bacteria target CD46, using it as a receptor or downregulating it in infected cells. Pathogenic Neisseria (N. gonorrhoeae and N. meningitidis) interact with epithelial cell CD46 at multiple levels. Infection via the Type IV pilus triggers its phosphorylation, alters its trafficking, and causes its secretion. We present evidence that Neisseria infection also stimulates its proteolytic processing by the endogenous protease complex Presenilin/¿- Secretase (PS/¿-S), an event that is linked to bacterial invasion. We present a model for PS/¿-S processing of CD46, and propose to test predictions arising from this model. Our overall goal is to provide a strong molecular framework for understanding the numerous regulatory activities of CD46, including its role in infection.

摘要 CD46是一种人类特有的膜蛋白，具有多种信号和受体特性。 尽管这种蛋白质具有多功能，但人们对其分子机制知之甚少。 它的生物学表型。几种病毒和细菌以CD46为靶标，将其用作受体或 在受感染的细胞中下调它。致病性奈瑟氏菌(淋病奈瑟菌和脑膜炎奈瑟菌)相互作用 上皮细胞CD46处于多个水平。通过IV型菌毛感染触发了它的磷酸化， 改变了它的贩运，并导致它的分泌。我们提出的证据表明奈瑟氏菌感染也 通过内源性酶复合体早老素/β-来刺激其蛋白降解过程。 分泌酶(PS/？-S)，一种与细菌入侵有关的事件。我们提出了一个PS/？模型--S CD46的处理，并建议测试由此模型产生的预测。我们的总体目标是 为了提供一个强大的分子框架来理解多种调控活动 CD46，包括它在感染中的作用。