GPCR-GIP networks: a first step in the discovery of new therapeutic drugs?
G protein-coupled receptors (GPCRs) are transmembrane molecules that, on interaction with G proteins upon ligand binding, can associate with a large variety of transmembrane or soluble proteins, termed 'GPCR-interacting proteins' (GIPs). Some special transmembrane GIPs are themselves GPCRs that form homo- or heterodimers, while other transmembrane GIPs are ionic channels, ionotropic receptors and single transmembrane proteins that control GPCR pharmacology and trafficking. Most soluble GIPs interact with the C-termini of GPCRs and often physically link GPCRs to large protein networks, called 'receptosomes', that include ionic channels, protein kinases, small G proteins, cytoskeletal proteins and adhesion molecules. Here, we review the nature and functions of some of these networks, such as the glutamate and serotonin receptosomes, and focus on the fine-tuning of GPCR signaling by GIPs. Finally, we discuss the possibilities for developing new therapeutic drugs capable of modulating GPCR signaling by disrupting or reinforcing specific GPCR-GIP interactions.
Bockaert
Joël
J
Laboratoire de Génomique Fonctionnelle, UPR CNRS 2580, 34094 Montpellier Cedex 5, France. joel.bockaert@ccipe.cnrs.fr
Dumuis
Aline
A
Fagni
Laurent
L
Marin
Philippe
P
D000818:Animals; D015195:Drug Design; D011992:Endosomes / Q000737:chemistry / Q000187:drug effects / Q000378:metabolism; D019204:GTP-Binding Proteins / Q000737:chemistry / Q000378:metabolism*; D006801:Humans; D043562:Receptors, G-Protein-Coupled / Q000737:chemistry / Q000378:metabolism*; D013678:Technology, Pharmaceutical / Q000379:methods / Q000639:trends
D043562:Receptors, G-Protein-Coupled; D019204:GTP-Binding Proteins