The changing world of G protein-coupled receptors: from monomers to dimers and receptor mosaics with allosteric receptor-receptor interactions.
Based on indications of direct physical interactions between neuropeptide and monoamine receptors in the early 1980s, the term receptor-receptor 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 receptor-receptor interactions in GPCR homodimers, heterodimers, and receptor mosaics. Stable heteromers of Class A receptors may be formed that involve strong high energy arginine-phosphate electrostatic interactions. These receptor-receptor 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.
Fuxe
Kjell
K
Department of Neuroscience, Karolinska Institutet, Stockholm, Sweden. Kjell.Fuxe@ki.se
Marcellino
Daniel
D
Borroto-Escuela
Dasiel Oscar
DO
Frankowska
Malgorzata
M
Ferraro
Luca
L
Guidolin
Diego
D
Ciruela
Francisco
F
Agnati
Luigi F
LF
D000494:Allosteric Regulation; D000818:Animals; D002118:Calcium / Q000378:metabolism; D002147:Calmodulin / Q000378:metabolism; D002462:Cell Membrane / Q000378:metabolism / Q000648:ultrastructure; D021962:Membrane Microdomains / Q000378:metabolism; D008958:Models, Molecular; D011487:Protein Conformation; D055503:Protein Multimerization; D043562:Receptors, G-Protein-Coupled / Q000737:chemistry* / Q000235:genetics / Q000378:metabolism*; D015398:Signal Transduction / Q000502:physiology*
D002147:Calmodulin; D043562:Receptors, G-Protein-Coupled; D002118:Calcium