ClickArr: a novel, high throughput assay for evaluating β-arrestin isoform recruitment

Modern methods for quantifying signaling bias at GPCRs rely on using a single {beta}-arrestin isoform. However, it is increasingly appreciated that the two {beta}-arrestin isoforms have unique roles, requiring the ability to assess {beta}-arrestin isoform preference. Herein, we present ClickArr, a live-cell assay that simultaneously reports recruitment of both {beta}-arrestin isoforms as they compete for interaction with GPCRs. We demonstrate that an agonist can have {beta}-arrestin isoform bias, potentially opening up a new dimension for drug development.