Multiplicity and regulation of G-protein couplings

During the last twenty years, molecular and biochemical data concerning G-protein coupled receptors have accumulated, providing a detailed characterisation of the structure and functions of this large family of receptors. Initially viewed as simple transducing proteins interacting with intracellular adapters which confer signalling specificity and amplification, the last decade has revealed the extreme complexity and flexibility offered by these membrane receptors. Indeed, there is accumulating evidence that these receptors can interact with several unrelated G-proteins and that some ligands can specifically orientate the functional response. This article summarizes my contributions to the study of the multiplicity and regulation of cell signallings associated with three unrelated systems: the neurotensin receptor, the type 1 metabotropic glutamate receptor and the type 1 cannabinoid receptor. Along with other studies, these experimental data emphasise on the importance of the emerging concept of functional selectivity which should lead to the development of drugs showing enhanced clinical efficacy with lower unwanted side effects.