The ‘magic tail’ of G protein-coupled receptors: an anchorage for functional protein networks

• Published in: FEBS Letters 2003-07, Vol.546 (1), p.65-72
• Main Authors: Bockaert, Joël, Marin, Philippe, Dumuis, Aline, Fagni, Laurent
• Format: Article
• Language: English
• Subjects: Allosteric Regulation; Animals; AT1, angiotensin II type 1; CN-Ras GEF, cyclic nucleotide-Ras guanine nucleotide exchange factor; CREB2, cAMP responsive element binding protein 2; DHPG, dihydroxyphenylglycine; Ena/VASP homology domain-containing protein; eNOS, endothelial nitric oxide synthase; EVH, Ena/VASP homology; G protein-coupled receptor; GABA-B, gamma-aminobutyric acid type B; GPCRs, G protein-coupled receptors; GTP-Binding Proteins - chemistry; GTP-Binding Proteins - metabolism; Humans; IP3, inositol trisphosphate; mGluR, metabotropic glutamate receptor; Models, Biological; NHERF, Na+/H+ exchanger regulatory factor (also called EBP ezrin-radixin-moesin binding protein); NMDA, N-methyl-D-aspartate; NR1, NR2, NMDA receptor 1, NMDA receptor 2; PDZ, PSD95-disc large-zona occludens; PICK-1, protein interacting with C kinase 1; PKC, protein kinase C; Protein Structure, Tertiary; PSD95, postsynaptic density protein of 95 kDa; PSD95-disc large-zona occludens domain-containing protein; PTH, parathyroid hormone; Receptor Cross-Talk; Receptors, Cell Surface - metabolism; Scaffolding; SH, Src homology; Shank, SH3 multiple ankyrin; Signal Transduction; Signaling; Targeting; TcTex-1, t-complex testis-expressed 1; β1 or β2-AR, β1 or β2 adrenergic receptors
• ISSN: 0014-5793; 1873-3468
• DOI: 10.1016/S0014-5793(03)00453-8

All cell types express a great variety of G protein-coupled receptors (GPCRs) that are coupled to only a limited set of G proteins. This disposition favors cross-talk between transduction pathways. However, GPCRs are organized into functional units. They promote specificity and thus avoid unsuitable cross-talk. New methodologies (mostly yeast two-hybrid screens and proteomics) have been used to discover more than 50 GPCR-associated proteins that are involved in building these units. In addition, these protein networks participate in the trafficking, targeting, signaling, fine-tuning and allosteric regulation of GPCRs. To date, proteins that interact with the GPCR C-terminus are the most abundant and are the focus of this review.