Indentification of novel molecular components at the cell periphery: taking advantage of EPEC pedestals

细胞外围新型分子成分的鉴定：利用 EPEC 基座

基本信息

批准号：
355316-2008
负责人：
Guttman, Julian
金额：
$ 2.55万
依托单位：
Simon Fraser University
依托单位国家：
加拿大
项目类别：
Discovery Grants Program - Individual
财政年份：
2012
资助国家：
加拿大
起止时间：
2012-01-01 至 2013-12-31
项目状态：
已结题

来源：
https://www.nserc-crsng.gc.ca/ase-oro/Details-Detailles_eng.asp?id=498117
关键词：
Indentification novel molecular components cell

项目摘要

The sub-cellular molecular events that occur at the cell periphery are crucial for organ development, maintaining cells and tissues, and healing. Aberrations to the "normal" functions of proteins within cells often lead to the manifestation of diseases. The cellular skeleton (the cytoskeleton) is a dynamic grouping of filamentous protein-based structures. In the majority of cells, the most prominently studied of these components are the actin filaments. These filaments are key sub-cellular elements involved in whole cell movement, transport of particles within cells, and the internalization of molecules from outside of the cell to the cell interior. During bacterial interactions with cells, these organisms often commandeer the cells for their own purposes. One of these bacteria, enteropathogenic E.coli (EPEC), remain outside of the host cells and inject bacterial proteins to control the host cell's functions. These bacteria continuously interact with the cell periphery and generate actin-rich structures (called "pedestals") at the bacteria/host cell contact points. Proteins identified at these sites are essential factors for normal cellular functions. In order to identify new proteins at the cell periphery, we will examine EPEC generated pedestals and exploit them as a model system. As pedestals are of uniform length and are relatively large, we will use advanced cell biological techniques to identify and functionally determine proteins in these structures. Newly identified proteins will be extensively characterized at pedestals and the cell periphery in motile as well as immotile cells. Through understanding the molecular components at the cell periphery, the work outlined in this proposal will generate profound insight into normal cellular physiology and will provide targets to examine during various diseases.

细胞周围发生的亚细胞分子事件对于器官发育，维持细胞和组织以及愈合至关重要。细胞内蛋白质的“正常”功能的畸变通常会导致疾病的表现。细胞骨架（细胞骨架）是基于丝状蛋白质结构的动态分组。在大多数细胞中，这些成分最突出的研究是肌动蛋白丝。这些细丝是全细胞运动，细胞内颗粒的转运以及分子从细胞外部到细胞内部的内在化。在细菌与细胞相互作用期间，这些生物通常是出于自己的目的指挥细胞。这些细菌之一，肠病e.coli（EPEC）留在宿主细胞外，并注入细菌蛋白，以控制宿主细胞的功能。这些细菌与细胞周围连续相互作用，并在细菌/宿主细胞接触点产生富含肌动蛋白的结构（称为“基座”）。在这些位点鉴定的蛋白质是正常细胞功能的重要因素。为了识别细胞外围的新蛋白质，我们将检查EPEC生成的基座并将其利用为模型系统。由于基座的长度均匀，并且相对较大，因此我们将使用先进的细胞生物学技术来识别并在这些结构中确定蛋白质。新近鉴定的蛋白质将在基座和摩托车和免疫细胞中的细胞周围广泛表征。通过了解细胞外围的分子成分，该提案中概述的工作将产生对正常细胞生理学的深刻见解，并将提供各种疾病期间检查的靶标。