Oligomerization of dopamine and serotonin receptors

Until recently, if has largely been assumed that G protein-coupled receptor s (GPCRs) function as monomeric entities. However, over the past few years, we and others have documented that GPCRs can form dimers and oligomers, le ading to a re-evaluation of the mechanisms thought ro mediate GPCR function . Despite the growing number of investigations into dimerization, little is known about the structural basis of receptor-receptor interactions and the functional consequences of dimer formation. Here, we present a brief revie w Of some insights we have gained into the dimerization of dopamine and ser otonin receptors. We have demonstrated that agonist-regulated trafficking i s identical for receptor monomers and dimers, however, agonist treatment ap pears to stabilise the receptor oligomers. An investigation of the structur al assembly between receptors involved in dimerization showed that there ar e several sites of interaction including hydrophobic transmembrane domain i nteractions and intermolecular disulphide bonds. We have also examined rece ptor heteroogliomerization and demonstrated the potential for novel functio ns as a result of these associations. Finally, as a result of these observa tions, we have been able to present evidence that GPCRs function as oligome rs in the cell. (C) 2000 American College of Neuropsychopharmacology. Publi shed by Elsevier Science Inc.