Methods for identifying compounds that regulate beta-arrestin signaling complexes
Researchers at Duke University have developed a a method to detect the formation of a specific beta-arrestin-biased signaling complex. After treatment with test compounds, murine brain striata were analyzed for the formation of a beta-arrestin-based signaling complex associated with dopamine receptor and chemokine receptor CXCR4 stimulation. Using this method, a compound that could block the formation of the beta-arrestin complex compound but had no effect on G-protein mediated signaling was identified. Further analysis demonstrated this compound has no effect in beta-arrestin-deficient mice. This assay can be applied to identify other compounds capable of blocking the formation of this beta-arrestin-based signaling to develop a new class of GPCR drugs that specifically target the alternative GPCR signaling pathway.