Molecular mechanisms underlying G protein coupled receptor signaling

维持活细胞的最佳健康和功能，从而维持整个生物体的最佳健康和功能，取决于细胞如何对不断轰击它们的大量物理和化学刺激作出反应。大多数化学刺激物，如激素和神经递质，不是通过直接进入细胞来传递它们的作用，而是通过与细胞表面称为受体的特定受体蛋白结合来传递。在一类称为G蛋白偶联受体的受体中，将信息传递到细胞内部涉及另一种称为G蛋白的蛋白质。这些受体是最丰富的细胞表面受体类型，并且形成了近50%的目前使用的治疗药物的靶标。因此，弄清这些成分是如何工作的，特别是了解它们在活细胞中是如何工作的，是极其重要的。该项目利用最先进的方法来研究受体及其同源G蛋白之间的相互作用，在活细胞中和实时。这项工作将回答有关G蛋白偶联受体信号传导性质的基本问题，并将有助于未来开发更有效的治疗药物。

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.