GPCR-GIP networks: a first step in the discovery of new therapeutic drugs?

Curr Opin Drug Discov Devel. 2004 Sep;7(5):649-57.


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.

Publication types

  • Research Support, Non-U.S. Gov't
  • Review

MeSH terms

  • Animals
  • Drug Design*
  • Endosomes / chemistry
  • Endosomes / drug effects
  • Endosomes / metabolism
  • GTP-Binding Proteins / chemistry
  • GTP-Binding Proteins / metabolism*
  • Humans
  • Receptors, G-Protein-Coupled / chemistry
  • Receptors, G-Protein-Coupled / metabolism*
  • Technology, Pharmaceutical / methods
  • Technology, Pharmaceutical / trends


  • Receptors, G-Protein-Coupled
  • GTP-Binding Proteins