GPCR interacting proteins (GIP).

G protein-coupled receptors (GPCR) interact not only with heterotrimeric G proteins but also with accessory proteins called GPCR interacting proteins (GIP). These proteins have important functions. They are implicated in GPCR targeting to specific cellular compartments, in their assembling into large functional complexes called "receptosomes," in their trafficking to and from the plasma membrane, and in the fine-tuning of their signaling properties. There are several types of GIPs. Some are transmembrane proteins such as another GPCR (homodimerization and heterodimerization), ionic channels, ionotropic receptors, and single transmembrane proteins. The latter is implicated in the fine-tuning of receptor pharmacology or signaling. Other GIPs are soluble proteins interacting mainly with the "magic" C-terminal tail. Among them, PDZ domain-containing proteins are the most abundant. They generally, but not always, interact with the extreme C-terminal domain of GPCRs. Some GIPs interact with specific sequences of the C-terminal such as the Homer binding sequence (-PPxxFR-), the dopamine receptor interacting protein (DRIP) binding sequence (-FxxxFxxxF-), etc. Finally, only few GIPs have been found thus far to interact with the third intracellular loop of GPCRs. The future will tell us if this situation is only due to technical reasons.