Formation of Cortical Plaques by Neisseria

描述(申请人提供)：奈瑟氏菌IV型菌毛调节 介导黏附和诱导细胞信号的细菌感染性 小路。一旦与其受体CD46结合，菌毛就会引起一过性 胞浆内游离钙离子水平升高，触发内小体和溶酶体 胞吐。纤毛细菌下一步触发微绒毛的伸长和 皮质膜上皮质膜斑块的形成 联系。皮质斑块包含跨膜的OpA受体簇 信号蛋白，肌动蛋白微丝和Ezrin，一种拴住 膜连接到肌动蛋白细胞骨架。这些斑块提供多种信号。 促进细菌感染的功能。与钙离子反应不同，钙离子反应可以 用纯净丸诱导，皮质斑块形成需要活体 双球菌和PILT，一种在菌毛组装和DNA中起作用的蛋白质 转型。PILT还控制毛发回缩，这是一个推动 抽搐运动和双球菌聚集成 微集落。回缩在衬底上产生很大的力 枕头是连在一起的。施加在真核生物细胞膜上的外力 细胞导致激酶级联反应，细胞骨架重组 以及翻译上的改动。质膜上产生的张力 因此，在感染过程中菌毛的回缩可以作为促进 皮质斑块的形成和随后的细菌入侵。基于 这些和其他的观察，我们提出了一个早期事件的模型 菌毛诱导的皮质斑块形成。在这份提案中，我们描述了 用实验来测试这个模型的关键预测。

DESCRIPTION (provided by the applicant): The Neisseria type IV pilus modulates bacterial infectivity by mediating adhesion and inducing cell signaling pathways. Upon binding its receptor, CD46, the pilus causes a transient increase in cytosolic free Ca2+ levels, triggering endosome and lysosome exocytosis. Piliated bacteria next trigger elongation of microvilli and formation of cortical plaques at the plasma membrane beneath the site of contact. Cortical plaques contain clusters of Opa receptors, transmembrane signaling proteins, actin microfilaments and ezrin, a protein that tethers the membrane to the actin cytoskeleton. These plaques serve multiple signaling functions that promote bacterial infection. Unlike the Ca2+ response, which can be induced with purified pill, cortical plaque formation requires live diplococci and PilT, a protein that functions in pilus assembly and DNA transformation. PilT also controls pilus retraction, a process that drives twitching motility and the ability of diplococci to aggregate into microcolonies. Retraction generates substantial force on the substrate to which the pilus is attached. External forces placed on the membranes of eucaryotic cells result in the induction of kinase cascades, cytoskeleton reorganization and alterations in translation. The tension generated on the plasma membrane by retraction of pili during infection may therefore act as a signal to promote the formation of cortical plaques and subsequent bacterial invasion. Based on these and other observations, we propose a model for early events in pilus-induced cortical plaque formation. In this proposal, we describe experiments to test key predictions of this model.