Role of Vinculin in Epithelial Cell Junctions

纽蛋白在上皮细胞连接中的作用

基本信息

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
项目类别：
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

项目摘要

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-基质粘附介导事件的细胞骨架调节以及在肿瘤疾病中这种调节被破坏的机制。细胞之间的粘附对于正常组织结构的建立和维持至关重要。因此，细胞与细胞的接触不仅在正常细胞生长和运动中具有重要功能，而且还与癌发生和转移过程中发生的失调有关。细胞有几种与其邻居相连的机制。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。尽管上皮细胞-细胞连接具有明显的稳定性，但它们是细胞的高度动态区域，可响应细胞外环境的提示。伴随对这些线索的反应而发生的形态变化是由潜在的肌动蛋白细胞骨架介导的，其特征和完整性由激酶、磷酸酶和小 GTP 酶控制。据报道，纽蛋白是一种重要的磷酸化蛋白，可将细胞间连接与肌动蛋白细胞骨架连接起来。纽蛋白在基质粘附位点的作用已被广泛研究多年，但纽蛋白在细胞与细胞接触位点的功能在很大程度上仍未被探索。本提案旨在回答这个问题。假设纽蛋白是上皮细胞连接的重要调节剂。该假设将得到检验，纽蛋白动力学及其磷酸化在粘附和紧密连接功能中的作用将得到检验。