Dimers of serotonin receptors: Impact on ligand affinity and signaling

Membrane receptors often form complexes with other membrane proteins that directly interact with different effectors of the signal transduction machinery. G-protein-coupled receptors (GPCRs) were for long time considered as single pharmacological entities. However, evidence for oligomerization appeared for various classes and subtypes of GPCRs. This review focuses on metabotropic serotonin (5-hydroxytryptamine, 5-HT) receptors, which belong to the rhodopsin-like class A of GPCRs, and will summarize the convergent evidence that homo- and hetero-dimers containing 5-HT receptors exist in transfected cells and in-vivo. We will show that complexes involving 5-HT receptors may acquire new signal transduction pathways and new physiological roles. In some cases, these complexes participate in disease-specific deregulations, that can be differentially affected by various drugs. Hence, selecting receptor complex-specific responses of these heterodimers may constitute an emerging strategy likely to improve beneficial therapeutic effects.