CD46 as a Signaling Intermediate in N. Gonorrhoeae Infection

摘要 CD 46是一种具有多种信号传导和受体特性的人类特异性膜蛋白。 尽管这种蛋白质具有多功能性，但对其分子机制知之甚少 其生物学表型的基础。几种病毒和细菌靶向CD 46，将其用作受体或 在受感染的细胞中下调。致病性奈瑟氏菌（N.淋病奈瑟菌和淋病奈瑟菌。脑膜炎）相互作用 上皮细胞CD 46在多个水平。通过IV型菌毛的感染触发其磷酸化， 改变了它的运输，并导致它的分泌。我们提出的证据表明，奈瑟菌感染也 通过内源性蛋白酶复合物早老素/早老素刺激其蛋白水解加工， 分泌酶（PS/S），与细菌入侵有关的事件。我们提出了一个模型PS/<$-S CD 46的处理，并提出测试从这个模型产生的预测。我们的总体目标是 为理解许多调节活动提供了一个强有力的分子框架， CD 46，包括其在感染中的作用。

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.