The changing world of G protein-coupled receptors: From monomers to dimers and receptor mosaics with allosteric receptorreceptor interactions

摘要

Based on indications of direct physical interactions between neuropeptide and monoamine receptors in the early 1980s, the term receptorreceptor interactions was introduced and later on the term receptor heteromerization in the early 1990s. Allosteric mechanisms allow an integrative activity to emerge either intramolecularly in G protein-coupled receptor (GPCR) monomers or intermolecularly via receptorreceptor interactions in GPCR homodimers, heterodimers, and receptor mosaics. Stable heteromers of Class A receptors may be formed that involve strong high energy argininephosphate electrostatic interactions. These receptorreceptor interactions markedly increase the repertoire of GPCR recognition, signaling and trafficking in which the minimal signaling unit in the GPCR homomers appears to be one receptor and one G protein. GPCR homomers and GPCR assemblies are not isolated but also directly interact with other proteins to form horizontal molecular networks at the plasma membrane.