β-Arrestin condensates regulate G-protein-coupled receptor function.

Anderson, Preston J; Xiao, Peng; Zhong, Ya-Ni; Kaakati, Adam N; Alfonso-DeSouza, Juliana; Patino, Alejandra; Ahn, Andrew; Jassal, Chanpreet et al. · Nature · 2026

basic_science · Level V

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Abstract

β-Arrestins 1 and 2 are multifunctional adaptor proteins<sup>1</sup> that regulate the signalling of G-protein-coupled receptors (GPCRs), the largest class of receptors, which impact nearly all aspects of physiology and are one of the most common drug targets<sup>2</sup>. Although β-arrestins interact with a wide array of signalling effectors at many GPCRs, it is unclear how β-arrestins promote such varied functions. Here we show that β-arrestins undergo liquid-liquid phase separation, forming condensates that regulate GPCR function. We show that condensation is specific to visual arrestins and β-arrestins, and demonstrate that β-arrestin oligomerization occurs in proximity to the GPCR to regulate GPCR functions such as internalization and signalling. Our work provides a paradigm for β-arrestin condensates as regulators of GPCR function, with liquid-liquid phase separation serving as an important promoter of signalling compartmentalization at GPCRs.