CHO-K1 cells stably expressing the µ opioid receptor were stimulated with known agonists and the MultiScreen β-arrestin assay run in a 384-well format.
With the expanding importance of β arrestin-mediated signaling and the role of biased signaling in GPCR physiology, robust β-arrestin cell-based assays have become a critical piece of GPCR -targeted drug development.
First generation β-Arrestin assays rely on tagging both the GPCR-of-interest and β-arrestin with fusion proteins that when brought together mediate production of light. Multispan’s proprietary MultiScreen β-Arrestin sensor technology relies on unmodified GPCRS and thus overcomes receptor-tagging drawback of first-generation technologies, enabling high-throughput detection of beta-arrestin translocation induced by native GPCRs in vitro and in vivo.
MultiScreen β-Arrestin assays use translocation of β-arrestin as the assay readout; however, it is β-arrestin and a membrane ‘sensor’ that are tagged rather than the GPCR of interest. Upon recruitment, tagged arrestin comes within proximity of a membrane sensor which in turns results in a functional luciferase enzyme.
This scheme overcomes receptor tagging drawbacks and importantly offers a means to examine β-arrestin activation via
endogenous or orphan GPCRs using an assay format well suited for high throughput, cell-based screening.
GPCR tagging, required by other β-Arrestin assays can be deleterious, induce receptor conformational changes, lead to
steric hinderance, or modify receptor pharmacology – all of which impact the identification and optimization of highly
qualified drug candidates. MultiScreen β-Arrestin Sensor Technology enables researchers to:
β-arrestin sensor technology is available as a portfolio of reagents, kits, and service to meet your specific assay needs:
MultiScreen™ β-Arrestin Assay Protocols: