Figure 1.

Schematic of functional selectivity at GPCRs. Cartoon model depicting various states of functional selectivity. Depending on the ligand and the induced receptor conformation, GPCRs are capable of signaling through the G-protein-mediated signaling pathway or the arrestin-mediated signaling pathway independently or simultaneously. Wacker et al (2013) crystalized for the first time, both the G-protein and arrestin state of serotonin receptor. Similarly, ligands can be antagonists for both pathways, or only one pathway while agonizing the other (collateral agonists). This structure-based signaling complexity is thought to give rise to multiple different downstream outputs, and may involve additional, currently uncharacterized effectors. As we increase our understanding of the molecular architecture of these signaling states, the development of novel psychiatric treatments that target these states will become increasingly more possible.