Regulation of Apical Traffic in Renal Epithelial Cells

肾上皮细胞顶端交通的调节

• 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
• 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

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。这部分是通过将新合成的和回收的膜蛋白靶向递送至顶端或基底外侧表面来实现的。顶端分选信号极其多样化，包括肽、脂质和聚糖依赖性基序。有趣的是，我们和其他实验室的最新数据表明，具有不同靶向信号的顶端蛋白在不同的运输载体群体中运输到表面。这些后高尔基体载体可以直接运输到细胞表面；然而，最近的研究表明，一些新合成的蛋白质在到达细胞表面的途中转运回收内体。我们的长期目标是识别指导新合成蛋白质顶端递送的信号，并了解这些信号在生物合成和内吞后途径的各个阶段如何被解释。该提案的目的是鉴定调节肾上皮细胞顶端表面不同途径的蛋白质，评估内吞区室在不同类别顶端蛋白的极化生物合成运输中的作用，并剖析沿生物合成和内吞后途径的聚糖依赖性分选机制。我们的研究结果将加深我们对生理相关分子的运输线索如何在不同的细胞内位点进行解释以实现正确分选的理解。 项目叙述 肾脏的主要功能是将水、离子和代谢物从形成的尿液中重吸收到血液中。肾细胞的表面被细分为不同的区域，这些区域面向尿液和血液，并且含有不同的蛋白质和脂质；表面成分的这种不对称分布对于肾功能的正常发挥至关重要。我们的目标是了解肾细胞如何创建和维持这些不同的表面区域。我们的研究结果将提供重要的基础信息，可用于设计潜在的疗法来对抗肾脏相关疾病，包括肾癌、急性肾衰竭和高血压。