G-protein-coupled receptor heterodimerization: assay technologies to clinical significance

The concept of G-protein-coupled receptor (GPCR) oligomerization has existed for many years, but has only recently received scrutiny from the pharmaceutical industry. The new interest in this theory has arisen not only because technologies to exploit GPCR oligomers are now available, but also because GPCR oligomerization has the potential to explain previously anomalous pharmacology and to provide an array of new therapeutic targets. The emergence of higher order GPCR organization adds a layer of complexity in the context of cellular control, and indeed drug discovery. This review outlines the current knowledge surrounding the oligomerization of GPCRs and describes effective assays for exploiting oligomerization in drug discovery. The clinical significance of oligomerization and the most promising strategies for therapeutically targeting GPCR oligomers are discussed.