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 概括 受体内吞作用是一种基本的细胞过程，可调节信号的质量和持续时间 转导。该项目使用基于系统的方法来评估内吞贩运 在免疫细胞中的两个受体（FCERI免疫受体和表皮生长因子受体）的 线。跨学科团队将检验以下假设：配体依赖于受体特异性信号传导 决定膜运输机制和途径选择的空间和时间调节。三 具体目的将检查如何：1）通过在质膜上选择性地将受体通过 依赖网状蛋白和独立途径； 2）内吞机械响应并受“输入”的调节 信号“来自受体货物；和3）受体信号传导由位置和特定相互作用控制 与内吞蛋白质。复杂的时空成像将跨越纳米范围，并将 与生化分析集成。实验数据集将在迭代基于规则的机理上为 和人口动态模型。该研究计划的结果将揭示有关途径的新信息 饱和度限制，限制组件的受体竞争以及其他参数不可能是 分别分析受体时被推断出来。