Protein-protein allosteric effects on cannabinoid receptor heteromer signaling

Type 1 and 2 cannabinoid receptors respond to endocannabinoids and contribute broadly to the function of the nervous system and immune system. Cannabinoid receptors participate in higher-order complex with other class A G protein-coupled receptors in both heterologous expression systems and native mammalian tissues. Receptor heteromers engage in protein-protein allosteric interactions that influence the conformation of receptor monomers within the complex. These altered conformations cause receptor heteromers to respond differently to cognate ligands compared to the individual receptors. This creates additional diversity in cell signaling that must be considered pharmacologically. In this chapter, we provide an overview of known cannabinoid receptor heteromers and signaling changes related to heteromer function. We also discuss the allosteric processes responsible for these effects and the therapeutic potential of this rapidly expanding group of receptor heteromers.