Congratulations: Dr. Kathryn Appleton new paper in Nature

  • Mar 23, 2016

The conformational signature of β-arrestin2 predicts its trafficking and signalling functions

Mi-Hye Lee, Kathryn M. Appleton, Erik G. Strungs, Joshua Y. Kwon, Thomas A. Morinelli, Yuri K. Peterson, Stephane A. Laporte & Louis M. Luttrell

Nature   doi:10.1038/nature17154
Received  Accepted    Published online   Excerpt: "Arrestins are cytosolic proteins that regulate G-protein-coupled receptor (GPCR) desensitization, internalization, trafficking and signalling12. Arrestin recruitment uncouples GPCRs from heterotrimeric G proteins, and targets the proteins for internalization via clathrin-coated pits34. Arrestins also function as ligand-regulated scaffolds that recruit multiple non-G-protein effectors into GPCR-based ‘signalsomes’56. Although the dominant function(s) of arrestins vary between receptors, the mechanism whereby different GPCRs specify these divergent functions is unclear. Using a panel of intramolecular fluorescein arsenical hairpin (FlAsH) bioluminescence resonance energy transfer (BRET) reporters7 to monitor conformational changes in β-arrestin2, here we show that GPCRs impose distinctive arrestin ‘conformational signatures’ that reflect the stability of the receptor–arrestin complex and role of β-arrestin2 in activating or dampening downstream signalling events."