Dynamics of Epithelial Polarity Proteins and the Control of Tissue Architecture

上皮极性蛋白的动力学和组织结构的控制

基本信息

批准号：
8535168
负责人：
James Todd Blankenship
金额：
$ 27.06万
依托单位：
UNIVERSITY OF DENVER (COLORADO SEMINARY)
依托单位国家：
美国
项目类别：
财政年份：
2011
资助国家：
美国
起止时间：
2011-09-01 至 2016-08-31
项目状态：
已结题

来源：
https://reporter.nih.gov/project-details/8535168
关键词：
Actomyosin Address Adhesions Apical Architecture Behavior Cell Adhesion Cell Polarity Cell membrane Cell surface Cell-Cell Adhesion Cells Cochlea Communities Complex Computational Technique Cytoskeleton Data Development Developmental Process Disease Drosophila genus E-Cadherin Embryo Environment Epithelial Epithelial Cells Epithelium Event Exocytosis F-Actin Funding Generations Genes Genetic Grant Green Algae Human Imaging Techniques Individual Intention Kinetics Life Maintenance Malignant Neoplasms Mediator of activation protein Membrane Membrane Protein Traffic Movement Mutation Neoplasm Metastasis Optics Organ Organism Palate Pathway interactions Positioning Attribute Process Property Proteins Reagent Research Role Shapes Site Skin Structure Techniques Tertiary Protein Structure Testing Tissues Vesicle Work aqueous intercalation molecular dynamics mutant new growth novel programs rab11 protein screening tissue repair tool trafficking

项目摘要

DESCRIPTION (provided by applicant): Dynamics of Epithelial Polarity Proteins and the Control of Tissue Architecture Epithelial sheets sit at the boundary of the organism and its external environment. The maintenance of these apical and basolateral domains is essential to the barrier function of epithelia, and the loss of apical-basal polarity is associated with the metastasis of many epithelial cancers. While epithelial sheets were once viewed as largely static assemblies, it is now appreciated that these are dynamic structures that can undergo significant reorganizing and renewal events. Indeed, cell neighbor exchange can be harnessed by developmental processes to effect changes in tissue architecture, and cell intercalation can drive epithelial tissue repair. In the Drosophila embryonic epithelium, individual cells are able to either consolidate cell-cell contacts or direct neighbor exchange movements through the asymmetric localization of cell adhesion and polarity proteins. While it is now apparent that actomyosin contraction drives the shrinking and loss of cell-cell interfaces, the means by which epithelial cells create new cell contacts and interfaces is unknown. The main question addressed in this project is the identification of the mechanism by which new cellular interfaces are established and maintained. We hypothesize that an early and essential event in the creation of the new interfaces that drive neighbor exchange will be directed membrane addition. The role of a key mediator of new membrane addition, the exocyst complex, in directing localized vesicular trafficking during tissue elongation will be characterized. We will also generate novel tools by drawing on recently created optical highlighter proteins that will allow the dynamic tracking of specific subpopulations of adhesion proteins. These tools and techniques should be useful to the general Drosophila community. Finally, genetic approaches are underway to identify new components involved in the establishment of distinct properties of cell polarity. The approaches used in these studies will draw on advanced imaging techniques that are just beginning to be applied to Drosophila. The funding of this project will be the first major grant for the newly established lab and will represent an important step towards the founding of an independent research program.

描述（由申请人提供）：上皮极性蛋白的动力学和组织结构上皮板的控制位于生物体及其外部环境的边界。这些顶端和基底外侧结构域的维持对于上皮的屏障功能至关重要，而顶质极性的丧失与许多上皮癌的转移有关。虽然上皮板曾经被视为在很大程度上是静态组件，但现在被认为是这些动态结构可以进行重大重组和更新事件。实际上，可以通过发育过程来利用细胞邻居的交换来影响组织结构的变化，并且细胞插入可以驱动上皮组织修复。在果蝇胚胎上皮中，单个细胞能够通过细胞粘附和极性蛋白的不对称定位巩固细胞 - 细胞接触或直接邻居交换运动。虽然现在很明显，肌动球蛋白收缩驱动细胞细胞界面的收缩和损失，但上皮细胞创建新的细胞接触和接口的手段尚不清楚。该项目中解决的主要问题是确定建立和维护新的细胞界面的机制。我们假设在创建驱动邻居交换的新界面中的早期和重要事件将被定向膜。新膜添加的关键介体（胞外复合物）在指导组织伸长过程中局部囊泡运输方面的作用将被表征。我们还将通过利用最近创建的光学荧光笔蛋白来生成新的工具，该蛋白将允许对粘附蛋白的特定亚群进行动态跟踪。这些工具和技术应该对果蝇一般社区有用。最后，正在进行遗传方法，以确定与细胞极性不同特性涉及的新组件。这些研究中使用的方法将利用刚刚开始应用于果蝇的先进成像技术。该项目的资金将是新成立的实验室的第一笔重大赠款，这将代表建立独立研究计划的重要一步。