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Molecular Mechanisms Regulating Epithelial Cell Apical Polarity and Ciliogenesis

调节上皮细胞顶端极性和纤毛发生的分子机制

基本信息

批准号：
10207607
负责人：
Rytis Prekeris
金额：
$ 33.76万
依托单位：
UNIVERSITY OF COLORADO DENVER
依托单位国家：
美国
项目类别：
财政年份：
2004
资助国家：
美国
起止时间：
2004-01-15 至 2024-06-30
项目状态：
已结题

来源：
https://reporter.nih.gov/project-details/10207607
关键词：
3-Dimensional Address Apical Architecture Binding Binding Proteins Biochemical Biochemistry Biological Assay Cell Culture Techniques Cell division Cell membrane Cells Cellular biology Cilia Complex Cues Cytokinesis Data Development Disease Docking Endosomes Epithelial Epithelial Cells Event Exhibits Funding Goals Homeostasis In Vitro Kidney Kidney Diseases Laboratories Location Mediating Modeling Molecular Morphogenesis Mutation Organogenesis Pathogenesis Play Polycystic Kidney Diseases Process Property Proteins Publishing Regulation Renal function Role Signal Transduction Site Structure Testing Tissues Transmembrane Transport Vertebral column Work Zebrafish base cilium biogenesis design imaging approach in vivo insight kidney cell kidney epithelial cell kinetosome mutant nephrogenesis novel polarized cell protein transport receptor tissue culture

项目摘要

Project Summary Epithelial cells exhibit remarkable apicobasal subcellular polarity that is essential for the proper functioning of epithelial tissues and allows epithelial cells to form a specialized apical structures, such as apical primary cilia. Finally, epithelial cells coordinate their polarization with neighboring cells to form an apical lumen, a key step in the establishment of renal architecture, and thereby function. Accordingly, mutations that disrupt function of molecules necessary for apicobasal polarization and apical cilia formation result in a variety of renal disorders, such as polycystic kidney disease (PKD). Thus, the overarching goal of this project is to characterize the molecular machinery coordinating apical lumen formation and ciliogenesis in kidney. To that end, we designed three specific aims. In the aim#1 we will analyze investigate the molecular machinery that determines where and when apical lumen forms and how that is coordinated with ciliogenesis. Specifically, we will test the role of newly identified polarity regulator Tbc1d1 in mediating lumenogenesis during kidney development. In the aim#2 we will dissect the coordination between the apical lumenogenesis and primary cilia formation/signaling. We recently identified Rab19 as Tbc1d1 binding protein and have shown that Rab19 is required for cilia formation. Thus, we will investigate the role of Rab19 in mediating cilia formation and targeting of cilia resident proteins. Finally, in aim#3 we will test dissect the mechanisms mediating kidney lumenogenesis and ciliogenesis in vivo using zebrafish. Completion of this project will provide a novel insight in understanding the molecular machinery and regulation of kidney epithelial cell polarization and cilia formation during normal epithelial tissue morphogenesis and in disease.

项目总结