Regulation of Apical Traffic in Renal Epithelial Cells

肾上皮细胞顶端交通的调节

基本信息

批准号：
7991693
负责人：
Ora A Weisz
金额：
$ 9.95万
依托单位：
UNIVERSITY OF PITTSBURGH AT PITTSBURGH
依托单位国家：
美国
项目类别：
财政年份：
2010
资助国家：
美国
起止时间：
2010-01-01 至 2010-12-31
项目状态：
已结题

来源：
https://reporter.nih.gov/project-details/7991693
关键词：
ADP-Ribosylation Factors Abbreviations Acute Kidney Failure Adaptor Signaling Protein Address Apical Binding Biochemical Blood Circulation Canis familiaris Carbohydrates Cell membrane Cell physiology Cell surface Cells Cues Data Diacylglycerol Kinase Disease Early Endosome Endosomes Epithelial Epithelial Cells Face Galectin 3 Glycolipids Glycosylphosphatidylinositols Goals Golgi Apparatus Guanine Nucleotide Dissociation Inhibitors Hemagglutinin Horseradish Peroxidase Hypertension Immunoglobulin A Individual Ion Transport Ions Kidney Laboratories Lactase Phlorizin Hydrolase Lectin Life Lipids Maintenance Mediating Membrane Membrane Microdomains Membrane Proteins Molecular Nerve Growth Factor Receptors Oligo-1,6-Glucosidase Pathway interactions Peptides Phosphatidylinositol 4,5-Diphosphate Phosphatidylinositols Phospholipase D Phosphotransferases Physiological Play Polymeric Immunoglobulin Receptors Polysaccharides Population Protein phosphatase Proteins Proteomics RNA Recycling Regulation Renal carcinoma Renal function Reporting Research Role Route Signal Transduction Site Small Interfering RNA Somatropin Sorting - Cell Movement Staging Stimulus Sucrase Surface System Testing Transferrin Transferrin Receptor Urine Vesicular stomatitis Indiana virus Water Wheat Germ Agglutinins cellular imaging cohort combat design endolyn genetic regulatory protein in vitro Assay kidney cell polarized cell response segregation sialomucin sialomucins targeted delivery trafficking trans-Golgi Network transcriptional coactivator p75 vesicular stomatitis virus G protein

项目摘要

DESCRIPTION (provided by applicant): Renal cell function requires the maintenance of polarized plasma membrane domains with distinct protein and lipid compositions. This is accomplished in part by the targeted delivery of newly synthesized and recycling membrane proteins to the apical or basolateral surface. Apical sorting signals are extraordinarily diverse and include peptide-, lipid- and glycan-dependent motifs. Interestingly, recent data from our and other laboratories suggest that apical proteins with different targeting signals traffic to the surface in distinct populations of transport carriers. These post-Golgi carriers may traffic directly to the cell surface; however, recent studies suggest that some newly-synthesized proteins transit recycling endosomes en route to the cell surface. Our long term goals are to identify the signals that direct apical delivery of newly- synthesized proteins, and to understand how these signals are interpreted at various stages along the biosynthetic and postendocytic pathways. The aims of this proposal are to identify proteins that regulate distinct pathways to the apical surface in renal epithelial cells, to assess the role of endocytic compartments in the polarized biosynthetic traffic of different classes of apical proteins, and to dissect the mechanism of glycan-dependent sorting along the biosynthetic and postendocytic pathways. The results of our studies will refine our understanding of how transport cues on physiologically relevant molecules are interpreted at distinct intracellular sites to enable proper sorting. PROJECT NARRATIVE The primary function of the kidney is the reabsorption of water, ions, and metabolites from the forming urine to the bloodstream. The surfaces of kidney cells are subdivided into different domains that face the urine and bloodstream and which contain distinct proteins and lipids; and this asymmetric distribution of surface components is essential for proper kidney function. Our goal is to understand how kidney cells create and maintain these distinct surface domains. The results of our research will provide critical basic information that can be applied to the design of potential therapies to combat kidney-related diseases including renal carcinoma, acute renal failure, and hypertension.

描述（由申请人提供）：肾细胞功能需要维持具有不同蛋白质和脂质组成的极化质膜结构域。这部分是通过针对新合成和回收膜蛋白到顶端或基底外侧表面的目标递送来完成的。顶部分类信号非常多样化，包括肽 - 脂质和糖依赖性基序。有趣的是，来自我们和其他实验室的最新数据表明，在不同的运输载体种群中，具有不同靶向信号的靶向信号的顶端蛋白质。这些高尔基载体可以直接流动到细胞表面。然而，最近的研究表明，一些新合成的蛋白质转运回收体在通往细胞表面的途径。我们的长期目标是确定直接直接递送新合成蛋白质的信号，并了解如何在生物合成和后观念途径的各个阶段解释这些信号。该提案的目的是鉴定蛋白质在肾上皮细胞中调节顶部表面的不同途径，以评估不同类别的顶端蛋白质的偏振生物合成性交通中的内吞区室的作用，以及沿着生物合成和终止途径的聚糖依赖性分类的机制。我们的研究结果将完善我们对如何在不同的细胞内部位解释生理相关分子的传输线索以实现适当分类的理解。项目叙述肾脏的主要功能是从形成的尿液到血液的水，离子和代谢产物的重吸收。肾细胞的表面被细分为面对尿液和血液的不同结构域，其中包含不同的蛋白质和脂质。表面成分的不对称分布对于适当的肾功能至关重要。我们的目标是了解肾细胞如何创建和维护这些不同的表面域。我们的研究结果将提供关键的基本信息，这些信息可以应用于潜在疗法的设计，以打击肾脏癌，急性肾衰竭和高血压在内的肾脏相关疾病。