A research team from Shandong University (SDU), in collaboration with scientists from Duke University in the United States, has published a study in the journal Nature revealing a key mechanism by which β-arrestin condensates regulate G-protein-coupled receptors (GPCRs) signaling.

The paper, entitled "β-Arrestin condensates regulate G-protein-coupled receptor function", was published online on May 27. Professors Sun Jinpeng and Xiao Peng of SDU and Professor Sudarshan Rajagopal of Duke University serve as co-corresponding authors. Xiao Peng and Zhong Yani from SDU are listed as co-first authors.

GPCRs form the largest family of membrane receptors in the human body and are important drug targets. However, how β-arrestins coordinate the complex spatial regulation of GPCR signaling has remained unclear.

The researchers found that endogenous β-arrestins can form dynamic, liquid-like condensates through liquid-liquid phase separation. These condensates help organize GPCR signaling complexes in specific cellular regions, enabling localized signal enrichment and precise regulation.

The study further shows that the intrinsically disordered C-terminal region of β-arrestin, together with oligomerization-driven multivalent interactions, is crucial for condensate formation. Disrupting this process impaired GPCR internalization and localized ERK signaling.

The findings provide a new framework for understanding GPCR-biased signaling and may offer fresh insights for drug development targeting neurological, metabolic and cancer-related diseases.