Molecular Mechanisms of G Protein-Coupled Receptor Cross Talk

所有活细胞的正常功能取决于它们如何对不断暴露的大量物理和化学刺激作出反应。大多数作用于细胞的化学刺激不是通过直接进入细胞，而是通过作用于细胞表面被称为受体的特定类型的受体蛋白。一个重要的受体家族通过与另一种称为G蛋白的蛋白质偶联将信息传递到细胞内部。这些G蛋白偶联受体正常功能的异常与多种疾病有关，如精神分裂症、疼痛和痴呆。迄今为止，大多数治疗这些疾病的治疗方法都是针对被认为在每种疾病状态中发挥作用的G蛋白偶联受体的个体类型，但这一方法取得了成败参半的成功。其中一个原因是，每种疾病实际上都涉及到不止一种类型的G蛋白偶联受体以复杂的方式与其他类型的受体交流。我们目前的建议特别关注一些新的机制，这些机制被认为在位于同一类型细胞的不同类型G蛋白偶联受体之间的通信中起重要作用。在这种情况下，了解这些受体蛋白如何相互沟通，对于揭示与维持健康、导致疾病的异常以及开发更有效的治疗方法有关的过程至关重要。

The normal function of all living cells depends on how they respond to the multitude of physical and chemical stimuli to which they are constantly exposed. The majority of chemical stimuli acting on cells do so not by directly entering the cell, but rather by acting on specific types of receiver proteins on the cell's surface called receptors. One important family of receptors transmit their message to the inside of the cell by coupling to yet another type of protein known as the G protein. Aberrations in the normal function of these G protein-coupled receptors have been implicated in a wide variety of disorders, such as schizophrenia, pain and dementia. To date, most therapeutic approaches to treating these disorders have targeted individual types of G protein-coupled receptors thought to play a role in each disease state, but this has met with mixed success. One of the reasons for this is that each disorder actually involves more than one type of G protein-coupled receptor communicating with other types in a complex way. Our current proposal specifically focuses on some of the newer mechanisms that have been suggested to play an important role in the communication between different types of G protein-coupled receptors located in the same type of cell. An understanding of how such receptor proteins can communicate with one another in this situation is absolutely vital in unravelling processes involved in the maintenance of health, abnormalities that lead to disease and in the development of more effective treatments.