betaarrestina

Beta-arrestins are a family of cytosolic proteins that regulate signaling by G protein-coupled receptors (GPCRs). In humans, the two main isoforms are beta-arrestin-1 (ARRB1) and beta-arrestin-2 (ARRB2). They bind to phosphorylated GPCRs after receptor activation, preventing further G protein signaling (desensitization) and promoting receptor internalization via clathrin-mediated endocytosis with adaptor proteins such as AP-2 and dynamin.

Beyond desensitization, beta-arrestins act as multifunctional scaffolds that assemble signaling complexes. They recruit kinases including ERK1/2, JNK, and p38 MAPK, enabling G protein–independent signaling. They can also mediate signaling from endosomes and, in some contexts, translocate to the nucleus to influence transcription factors. This dual role allows GPCRs to continue signaling through alternative pathways even after G protein coupling is reduced.

Physiological roles of beta-arrestins are broad, spanning cardiovascular, nervous system, metabolic, and immune function. They contribute to processes such as sensation, synaptic transmission, and hormone signaling. In pharmacology, beta-arrestin pathways have been implicated in opioid analgesia and tolerance, and the concept of biased agonism has emerged, where ligands preferentially activate beta-arrestin–dependent versus G protein–dependent signaling. This distinction informs drug development with the aim of maximizing therapeutic benefit while minimizing adverse effects.

Clinical relevance centers on the involvement of beta-arrestin signaling in various GPCR-related conditions and its exploration as a therapeutic target. Researchers study beta-arrestins to understand receptor regulation, signaling diversity, and ways to modulate these pathways for clinical use.