Role of Vinculin in Epithelial Cell Junctions

纽蛋白在上皮细胞连接中的作用

• 批准号: 7114407
• 负责人: Kris A DeMali
• 金额: $ 13.23万
• 依托单位: UNIVERSITY OF IOWA
• 依托单位国家: 美国
• 财政年份: 2005
• 资助国家: 美国
• 起止时间: 2005-08-19 至 2010-07-31
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/7114407
• 关键词: Role; Vinculin; Epithelial; Cell; Junctions

DESCRIPTION (provided by applicant): The long-term goal of this research is to investigate the cytoskeletal regulation of cell-cell and cell-matrix adhesion-mediated events and the mechanism by which this regulation is subverted in neoplastic disease. The adhesion of cells to one another Is essential for the establishment and maintenance of normal tissue architecture. As such cell-cell contacts not only have an essential function in normal cell growth and motility but are also involved in cases of dysregulation that occur during carcinogenesis and metastasis. Cells have several mechanisms for linking to their neighbors. These so-called "cell junctions" consist of proteins that assemble into a variety of structures such as gap junctions, tight junctions, adherens junctions, desmosomes and hemidesmosomes, each with a different function. Despite their apparent stability, epithelial cell-cell junctions are highly dynamic regions of a cell that respond to cue from the extracellular environment. The morphological changes accompanying the response to these cues are mediated by the underlying actin cytoskeleton and their characteristics and integrity is controlled by kinases, phosphatases and small GTPases. A prominent phosphorylated protein that is reported to link cell-cell junctions to the actin cytoskeleton is vinculin. The role of vinculin at sites of adhesion to the matrix has been widely studied for many years, but the function of vinculin at sites of cell-cell contact remains largely unexplored. This proposal is directed towards answering this question. The hypothesis is that vinculin is an important regulator of epithelial cell junctions. This hypothesis will be tested and the role of vinculin dynamics and its phosphorylation in adherens and tight junction function will be examined.

描述（由申请人提供）：这项研究的长期目标是研究细胞细胞和细胞 - 矩阵粘附介导的事件的细胞骨架调节，以及该调节在肿瘤疾病中颠覆的机制。细胞彼此的粘附对于建立和维持正常组织结构至关重要。由于这种细胞 - 细胞接触不仅在正常细胞生长和运动中具有重要功能，而且还参与了癌变和转移过程中发生失调的病例。细胞具有与邻居联系的几种机制。这些所谓的“细胞连接”由蛋白质组成，这些蛋白质组装成各种结构，例如间隙连接，紧密连接，粘附连接，脱骨小体和Hemidesmosomes，每个结构具有不同的功能。尽管具有明显的稳定性，但上皮细胞 - 细胞连接是细胞的高度动态区域，它会从细胞外环境中响应提示。伴随对这些线索的反应的形态变化是由基础肌动蛋白细胞骨架介导的，其特征和完整性受激酶，磷酸酶和小GTPases的控制。据报道将细胞 - 细胞连接与肌动蛋白细胞骨架联系起来的突出的磷酸化蛋白是vinculin。多年来已经广泛研究了Vinculin在粘附部位对基质的粘附部位的作用，但是Vinculin在细胞细胞接触部位的功能在很大程度上尚未探索。该提案是针对回答这个问题的。假设是，Vinculin是上皮细胞连接的重要调节剂。该假设将进行检验，并且将研究Vinculin动力学及其在粘附剂和紧密连接功能中的磷酸化的作用。