Molecular mechanisms underlying G protein coupled receptor signaling

维持活细胞的最佳健康和功能，进而维持整个生物体的健康和功能，取决于细胞如何对持续轰炸它们的多种物理和化学刺激做出反应。大多数化学刺激，如激素和神经递质，不是通过直接进入细胞来发挥作用，而是通过与细胞表面称为受体的特定受体蛋白结合来发挥作用。在一类被称为G蛋白偶联受体的受体中，信息传递到细胞内部涉及另一种名为G蛋白的蛋白质。这些受体是最丰富的细胞表面受体类型，构成了目前使用的近50%治疗药物的靶标。因此，了解这些成分是如何工作的是极其重要的，尤其是要知道它们在活细胞中是如何工作的。该项目利用最先进的方法，在活细胞中实时检测受体与其同源G蛋白之间的相互作用。这项工作将回答有关G蛋白偶联受体信号的本质的基本问题，并将有助于未来更有效的治疗剂的开发。

The maintenance of optimum health and function of living cells, and consequently that of the whole organism, depends on how cells respond to a multitude of physical and chemical stimuli that continually bombard them. The majority of the chemical stimuli such as hormones and neurotransmitters impart their actions not by directly entering the cell, but instead, by binding to a specific receiver protein at the cell surface called a receptor. In one class of such receptors called G protein-coupled receptors, the transmission of the message to the interior of the cell involves yet another protein called G protein. These receptors are the most abundant type of cell surface receptors and form the targets for nearly 50% of currently used therapeutic drugs. It is, therefore, extremely important to unravel how each of these components works, and in particular to know how they work in living cells. This project utilizes state-of-the-art methodologies to examine interactions between receptors and their cognate G proteins, in living cells and in real-time. The work will answer fundamental questions about the nature of G protein-coupled receptor signaling and will aid in the future development of more effective therapeutic agents.