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

项目3 Angela Wandinger-Ness，Pi 摘要 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。该项目使用了一种基于系统的方法来比较评估细胞内转运 免疫细胞中的两种受体(FceRI免疫受体和表皮生长因子受体ErbB1) 排队。跨学科研究小组将测试这一假设，即依赖于配体的受体特异性信号 决定膜运输机制和途径选择的空间和时间调节。三 特定的目标将研究：1)受体如何选择性地内化在质膜上 依赖于笼状蛋白的和独立的途径；2)内吞机制对“输入”作出反应并受其调节 来自受体货物的信号；3)受体信号受位置和特定相互作用的控制 含有内吞蛋白。复杂的时空成像将跨越纳米到微米级，并将是 与生化分析相结合。实验数据集将迭代地告知基于规则的机械论 和人口动力学模型。这项研究计划的结果将揭示有关路径的新信息 饱和极限，受体对限制性成分的竞争，以及其他参数，这不能 在单独分析受体时推断出来的。

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.