Role of Vinculin in Epithelial Cell Junctions

纽蛋白在上皮细胞连接中的作用

• 批准号: 7273730
• 负责人: Kris A DeMali
• 金额: $ 15.39万
• 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/7273730
• 关键词: Actins; Address; Adherens Junction; Adhesions; Architecture; Area; Binding; Biochemical; Cell Adhesion; Cell Line; Cell-Cell Adhesion; Cell-Matrix Junction; Cells; Characteristics; Chickens; Cues; Cytoskeleton; Desmosomes; Disease; Disruption; Environment; Epithelial Cell Junction; Epithelial Cells; Event; Gap Junctions; Goals; Hemidesmosomes; Human; Intercellular Junctions; Invaded; Link; Maintenance; Mediating; Modification; Monomeric GTP-Binding Proteins; Neoplasm Metastasis; Normal Cell; Normal tissue morphology; Phosphoric Monoester Hydrolases; Phosphorylation; Phosphotransferases; Property; Proteins; Regulation; Reporting; Research; Role; Serine; Shigella; Shigella Infections; Site; Small Interfering RNA; Structure; Testing; Threonine; Tight Junctions; Tumor Cell Invasion; Tyrosine Phosphorylation; Vinculin; carcinogenesis; cell growth; cell motility; domain mapping; extracellular; mutant; neoplastic; pathogen; protein protein interaction; response

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）：本研究的长期目标是研究细胞-细胞和细胞-基质粘附介导的事件的细胞骨架调节，以及这种调节在肿瘤性疾病中被破坏的机制。细胞之间的粘附对于正常组织结构的建立和维持是必不可少的。因此，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，而且还涉及在癌发生和转移期间发生的失调情况。细胞有几种连接到邻居的机制。这些所谓的“细胞连接”由组装成各种结构的蛋白质组成，例如间隙连接、紧密连接、粘附连接、桥粒和半桥粒，每种结构具有不同的功能。尽管它们表面上稳定，上皮细胞-细胞连接是细胞的高度动态区域，其响应于来自细胞外环境的提示。伴随着对这些线索的响应的形态学变化由潜在的肌动蛋白细胞骨架介导，并且它们的特征和完整性由激酶、磷酸酶和小GTP酶控制。据报道，将细胞-细胞连接到肌动蛋白细胞骨架的突出的磷酸化蛋白质是黏着斑蛋白。黏着斑蛋白在基质粘附位点的作用已被广泛研究多年，但黏着斑蛋白在细胞-细胞接触位点的功能仍未被探索。本建议旨在回答这一问题。该假说认为黏着斑蛋白是上皮细胞连接的重要调节因子。这一假设将被测试和黏着斑蛋白动力学及其磷酸化的作用，在粘附和紧密连接功能将被检查。