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Abstract Arrestins are a family of intracellular proteins that includes two visual arrestins (Arrestin 1 and Arrestin 4) and two non-visual arrestins, defined as Arrestin 3 (or β-Arr1) and Arrestin 2 (or β-Arr3). Both β- Arr1& β-Arr2 genes are widely expressed in most types of mammalian cells. They are known with their regulatory role in G protein coupled receptors (GPCRs) desensitization. Thus, decrease their working activities could induce signal termination. Liganded (signal stimulated) GPCRs are internalized through a mechanism involving arrestindependent binding to clathrin-coated pits. This clathrin mediated endocytosis (CME) is the most common endocytic mechanism, used in receptor internalization and involves a subset of regulatory and scaffolding proteins including clathrin, β-arrestins, dynamine and some adaptor proteins (called Adaptins). Subsequent studies have introduced β- Arrs as a part of the multi-protein complex (receptorsome) involved in targeting receptor kinase complex to clathrin-coated pits followed by receptor internalization. Moreover, β-Arrs mediates other pathways distinct from the G protein-dependent activation. |