Activation mechanism of neurotransmitter G protein coupled receptors  

作　　者：刘剑峰[1] 

机构地区：[1]教育部分子生物物理重点实验室、华中科技大学生命科学与技术学院,武汉430074

出　　处：《中国药理学通报》2015年第B11期4-4,共1页Chinese Pharmacological Bulletin

基　　金：国家自然科学基金杰出青年科学基金（31225011）;国家自然科学基金重点项目（31130028）.

摘　　要：G-protein coupled receptors （GPCRs） class C represent a distant group among the large family of GPCRs. This class includes the receptors for the main neurotransmitters, glutamate and gamma-aminobutyric acid （GABA）, and the receptors for Ca2＋, some taste and pheromone molecules, as well as some orphan receptors. Like any other GPCRs, these receptors possess a heptahelical domain （HD） involved in heterotrimeric G-protein activation, but most of them also have a large extracellular domain （VFT） responsible for agonist recognition and binding. These receptors are dimers, either homo or heterodimers. Then whereas have mGluRs is homodimers, GABAB receptor was the first heteromeric G-protein coupled receptor （GPCR） identified. Indeed, both GB1 and GB2 subunits appear necessary to get a functional GABAB receptor. We have demonstrated that the interactions be- tween VFT domain of both GB1 and GB2 were important for receptor activation. We have also shown the dynamic movement of trans-membrane of mGluRs within dimers. Then we have found that the GABAB receptor induced acti- vation of ERK1/2/CREB and protected neurons from apoptosis by trans-activating IGF-1R. We have also demon- strated that GABAB receptor activation has been modulated by the dynamic protein-protein interactions between re- ceptors and its downstream signal proteins such as FAK1 and Rap l. Finally, we have performed the HTS screening and found the first negative allosteric modulator for GABAB receptors.

关 键 词：MARINE LYSOZYME SUPPOSITORY BACTERIAL VAGINITIS 

分 类 号：R[医药卫生]