Microscopic methods to study how GPCR dynamics and localization impact signaling specificity (C03+)

我们的项目将解决gpcr的亚细胞定位如何影响其功能的问题：我们将(i)描述受体、g蛋白及其动态耦合的异质分布；（ii）分析受体、G蛋白和配体对这种异质性的依赖性（iii）研究受体相互作用蛋白和局部膜曲率的影响。我们将使用β-肾上腺素能受体（β1和β2AR）、神经肽y受体（NPY2R）和毒蕈碱乙酰胆碱受体（M2R）作为模型。我们将结合工具，如荧光标记蛋白质和传感器与单分子跟踪，图像相关光谱学和随机定位显微镜。然后，我们将应用我们的方法来研究心肌细胞中受体及其信号的区隔化。

Our project will address the question of how the subcellular localization of GPCRs affects their function: We will (i) describe the heterogeneous distribution of receptors, G-proteins and their dynamic coupling; (ii) analyze the dependence Receptors-, G proteins- and ligands-dependence on such heterogeneity (iii) investigate the effect of receptor-interacting proteins and local membrane curvature. As models we will use β-adrenergic receptors (β1 and β2AR), Neuropeptide Y-Receptors (NPY2R) und Muscarinic Acetylcholine Receptors (M2R). We will combine tools such as fluorescently labeled proteins and sensors with Single Molecule Tracking, Image Correlation Spectroscopy and Stochastic Localization Microscopy. We will then apply our approaches to study the compartmentalization of the receptors and their signals in Cardiac Myocytes.