betaarrestinas

Beta-arrestins are a family of cytosolic proteins that regulate signaling through G protein-coupled receptors (GPCRs). In mammals the two best characterized paralogs are beta-arrestin-1 (ARRB1) and beta-arrestin-2 (ARRB2). They are widely expressed across tissues and participate in multiple aspects of GPCR regulation.

Beta-arrestins perform several core roles. They bind to activated and phosphorylated GPCRs, effectively preventing further coupling to G proteins and thereby desensitizing the receptor. They also act as adaptor proteins that recruit clathrin and AP-2, promoting receptor internalization into endosomes and influencing whether receptors are recycled back to the surface or degraded. In addition to these regulatory tasks, beta-arrestins serve as scaffolds for signaling complexes, enabling G protein–independent pathways such as mitogen-activated protein kinase (MAPK) cascades (e.g., ERK, JNK, p38) and other kinase or second messenger networks.

This dual capacity—terminating G protein signaling while enabling alternative signaling—underpins the concept of biased agonism, where different ligands preferentially activate either G protein–mediated or arrestin-mediated pathways. The functions of beta-arrestins have broad implications for physiology and pharmacology, influencing cardiovascular regulation, pain, metabolism, and neurological processes. Because of their central role in GPCR signaling, beta-arrestins are considered potential targets for drugs designed to modulate receptor activity with improved therapeutic profiles and reduced adverse effects.