Arrestin

Arrestin is a key protein that regulates G protein-coupled receptor (GPCR) signaling. Upon ligand activation, GPCRs undergo C-terminal phosphorylation by specific kinases (such as GRK, G protein-coupled receptor kinase), which recruits Arrestin, thereby preventing further coupling between GPCRs and G proteins while triggering receptor internalization and downstream signal transduction. Arrestin plays a crucial role in signal transduction, receptor desensitization and endocytosis, as well as multiprotein signaling complex assembly.
Arrestin is mainly classified into four types: Visual Arrestin (Arrestin-1), Cone Arrestin (Arrestin-4), β-Arrestin 1 (Arrestin-2), and β-Arrestin 2 (Arrestin-3). Among them, Arrestin-1 and Arrestin-4 are primarily involved in retinal phototransduction, whereas β-Arrestin 1 and β-Arrestin 2 are widely expressed in multiple tissues, regulating most GPCR-related signaling pathways. Structurally, Arrestin consists of N-terminal and C-terminal β-strand domains, stabilized by a polar core, and undergoes conformational changes upon receptor binding, thereby initiating signal transmission.
In the nervous system, Arrestin regulates dopamine receptor (e.g., D2 receptor) signaling, affecting Parkinson’s disease and Schizophrenia. In cancer, Arrestin integrates ERK, JNK, and Akt signaling pathways to regulate tumor cell growth and migration, for example, β-Arrestin 2-mediated GPCR signaling promotes cancer cell survival and drug resistance. Additionally, Arrestin is involved in inflammatory responses and immune regulation, playing important roles in diabetes, asthma, and inflammatory diseases^[1][2].