arrestiinien

Arrestins are a small family of cytosolic proteins that regulate signaling by G protein–coupled receptors (GPCRs). In vertebrates, the arrestin family includes visual arrestins (arrestin-1, also known as S-arrestin, expressed in rod photoreceptors, and cone arrestin, sometimes called arrestin-4) and non-visual arrestins (beta-arrestin-1 and beta-arrestin-2). The primary role of arrestins is to desensitize GPCR signaling: when a GPCR is phosphorylated by GPCR kinases (GRKs), arrestins bind to the receptor and prevent further activation of G proteins. This binding also promotes receptor internalization via clathrin-coated pits, aiding receptor endocytosis and trafficking to endosomes.

Beyond termination of G protein signaling, arrestins function as scaffolds that assemble signaling complexes. This scaffolding can activate or modulate alternative pathways, such as mitogen-activated protein kinase (MAPK) cascades, providing signaling routes that can be distinct from those initiated directly by G proteins. Arrestins also influence receptor resensitization by facilitating receptor recycling back to the plasma membrane.

Different arrestins have specialized roles. Visual arrestins regulate phototransduction in the retina, helping to terminate light-evoked signals in rods and cones. Beta-arrestins regulate a wide range of GPCRs, contributing to receptor trafficking, signaling to various intracellular pathways, and effects on gene expression and cytoskeletal organization.

Structural studies reveal a two-domain conformation with a polar core that recognizes phosphorylated receptor tails. Genetic and biochemical research continues to define the diverse functions of arrestins, including potential clinical implications, such as modulating cardiovascular and neuropsychiatric signaling through GPCR pathways.