Gprotein 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 gammaaminobutyric 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 Gprotein 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 Gprotein coupled receptor (GPCR) identified.Indeed, both GB1 and GB2 subunits appear necessary to get a functional GABAB receptor.We have demonstrated that the interactions between VFT domain of both GB1 and GB2 were important for receptor activation.We have also shown the dynamic movement of transmembrane of mGluRs within dimers.Then we have found that the GABAB receptor induced activation of ERK1/2/CREB and protected neurons from apoptosis by transactivating IGF1R.We have also demonstrated that GABAB receptor activation has been modulated by the dynamic proteinprotein interactions between receptors and its downstream signal proteins such as FAK1 and Rapl.Finally, we have performed the HTS screening and found the first negative allosteric modulator for GABAB receptors.