G Protein-Coupled Receptor Heteromers

Annu Rev Pharmacol Toxicol. 2016:56:403-25. doi: 10.1146/annurev-pharmtox-011613-135952. Epub 2015 Oct 22.


G protein-coupled receptors (GPCRs) compose one of the largest families of membrane proteins involved in intracellular signaling. They are involved in numerous physiological and pathological processes and are prime candidates for drug development. Over the past decade, an increasing number of studies have reported heteromerization between GPCRs. Many investigations in heterologous systems have provided important indications of potential novel pharmacology; however, the physiological relevance of these findings has yet to be established with endogenous receptors in native tissues. In this review, we focus on family A GPCRs and describe the techniques and criteria to assess their heteromerization. We conclude that advances in approaches to study receptor complex functionality in heterologous systems, coupled with techniques that enable specific examination of native receptor heteromers in vivo, are likely to establish GPCR heteromers as novel therapeutic targets.

Keywords: allosterism; biochemical fingerprint; bivalent ligands; dimerization; heterodimerization; oligomers; proximity-based assays.

Publication types

  • Research Support, N.I.H., Extramural
  • Research Support, Non-U.S. Gov't
  • Review

MeSH terms

  • Animals
  • Drug Discovery / methods
  • Humans
  • Membrane Proteins / metabolism
  • Receptors, G-Protein-Coupled / metabolism*
  • Signal Transduction / physiology


  • Membrane Proteins
  • Receptors, G-Protein-Coupled