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.

抽象的 CD46是一种具有许多信号传导和受体特性的人特异性膜蛋白。 尽管该蛋白质具有多功能性，但对分子机制知之甚少 其生物学表型的基础。几种病毒和细菌靶向CD46，使用它作为接收器或 在感染细胞中下调它。致病性奈瑟氏菌（N. Gonorrhoeae和N. Meningitidis）相互作用 上皮细胞CD46在多个水平上。通过IV型Pyrus感染会触发其磷酸化， 改变其贩运，并引起其分泌物。我们提供了奈瑟氏菌感染的证据 通过内源性蛋白酶复合蛋白/�-刺激其蛋白水解加工 - 分泌酶（PS/¿-S），与细菌侵袭有关的事件。我们提出了PS/¿-S的模型 CD46的处理以及测试由该模型产生的预测的建议。我们的总体目标是 提供一个强大的分子框架来理解 CD46，包括其在感染中的作用。