Research Project 3: Dissecting the spatio-temporal coordination of endocytic traf

研究项目3：剖析内吞运输的时空协调

• 批准号: 8919390
• 负责人: Angela Wandinger-Ness
• 金额: $ 24.44万
• 依托单位: UNIVERSITY OF NEW MEXICO HEALTH SCIS CTR
• 依托单位国家: 美国
• 财政年份: 2009
• 资助国家: 美国
• 起止时间: 2009-08-01 至
• 项目状态: 未结题
• 来源: https://reporter.nih.gov/project-details/8919390
• 关键词: Biochemical; Cell Line; Cell membrane; Cell physiology; Cells; Clathrin; Complex; Comprehension; Coupled; Coupling; Data Set; Disease; Endocytosis; Endosomes; Epidermal Growth Factor Receptor; Event; Feedback; Genetic; Genetic Screening; Goals; Hematopoietic; Image; Immune; Immune System Diseases; Immune response; Investigation; Ligands; Link; Location; Measures; Mediating; Membrane; Membrane Protein Traffic; Microscopy; Modeling; Neurologic; Organ; Outcomes Research; Output; Pathway interactions; Physiological; Population Dynamics; Process; Proteins; Receptor Protein-Tyrosine Kinases; Receptor Signaling; Regulation; Research Project Grants; Side; Signal Transduction; Specialist; System; Systems Biology; Testing; Time; Tissues; Work; base; cancer stem cell; imaging modality; innovation; insight; mathematical model; membrane model; nano; novel; quantitative imaging; receptor; response; skills; spatial relationship; spatiotemporal; stem cell niche; trafficking

Project 3 Angela Wandinger-Ness, PI Summary Receptor endocytosis is a fundamental cellular process that regulates the quality and duration of signal transduction. This project uses a systems-based approach to comparatively evaluate the endocytic trafficking of two receptors (FceRI immunoreceptor and the Epidermal Growth Factor Receptor, erbB1) in an immune cell line. The interdisciplinary team will test the hypothesis that ligand-dependent, receptor-specific signaling dictates spatial and temporal regulation of membrane trafficking machinery and pathway selection. Three specific aims will examine how: 1) receptors are selectively internalized at the plasma membrane through clathrin-dependent and independent pathways; 2) endocytic machinery responds to and is regulated by "input signals" from receptor cargo; and 3) receptor signaling is controlled by location and via specific interactions with endocytic proteins. Sophisticated spatiotemporal imaging will span nano to micron scales and will be integrated with biochemical analyses. The experimental data sets will iteratively inform rule-based mechanistic and population dynamics models. Outcomes from this research plan will reveal new information on pathway saturation limits, receptor competition for limiting components, among other parameters, that cannot be extrapolated when analyzing receptors individually.

项目3 Angela Wandinger-Ness，PI 总结 受体内吞作用是调节信号质量和持续时间的基本细胞过程 转导本项目采用基于系统的方法来比较评估内吞运输 免疫细胞中的两种受体（FceRI免疫受体和表皮生长因子受体，erbB 1） 线这个跨学科的团队将测试配体依赖性、受体特异性信号传导 决定了膜运输机制和途径选择的空间和时间调节。三 具体的目标将研究：1）受体是如何选择性地内化在质膜上，通过 网格蛋白依赖性和非依赖性途径; 2）内吞机制响应于“输入”并受其调节 受体信号传导受位置和特异性相互作用的控制 与内吞蛋白质。复杂的时空成像将跨越纳米到微米尺度， 与生化分析相结合。实验数据集将迭代地通知基于规则的机制 人口动态模型。这项研究计划的结果将揭示有关途径的新信息 饱和极限，受体对限制成分的竞争，以及其他参数，这些参数不能 当单独分析受体时推断。