Arrestins

Abstract

Arrestins specifically bind active phosphorylated G protein-coupled receptors (GPCRs). Receptor binding induces the release of the arrestin C-tail, which in non-visual arrestins contains high-affinity binding sites for clathrin and its adaptor AP2. Thus, serving as a physical link between the receptor and key components of the internalization machinery of the coated pit is the best-characterized function of non-visual arrestins in GPCR trafficking. However, arrestins also regulate GPCR trafficking less directly by orchestrating their ubiquitination and deubiquitination. Several reports suggest that arrestins play additional roles in receptor trafficking. Non-visual arrestins appear to be required for the recycling of internalized GPCRs, and the mechanisms of their function in this case remain to be elucidated. Moreover, visual and non-visual arrestins were shown to directly bind N-ethylmaleimide-sensitive factor, an important ATPase involved in vesicle trafficking, but neither molecular details nor the biological role of these interactions is clear. Considering how many different proteins arrestins appear to bind, we can confidently expect the elucidation of additional trafficking-related functions of these versatile signaling adaptors.

An Approach to Spatiotemporally Resolve Protein Interaction Networks in Living Cells

“…Arrestin3 is critical to both B2AR and DOR function and associates transiently following agonist stimulation (Gurevich and Gurevich, 2015). Due to the nature of this interaction, co-immunoprecipitation of arrestin3 with GPCRs often requires additional crosslinking (Cheng et al, 2000; Luttrell et al, 1999; Perry et al, 2002).…”

Expression and light-dependent translocation of β-arrestin in the visual system of the terrestrial slug Limax valentianus

“…Indeed, the difference between the binding affinities for the active and inactive phosphorylated GPCRs is greater in visual arrestin than in β-arrestin in vertebrates (Celver et al, 2002). This suggests a more efficient dissociation of visual arrestin from phosphorylated inactive opsins, probably allowing visual arrestin to do the next round of opsin signaling termination as well as rapid dephosphorylation of opsins by phosphatases for their reuse (Gurevich and Gurevich, 2015). It would be intriguing to see whether a similar kinetic difference exists between visual and β-arrestin in arthropods and cephalopods.…”

Endocrinology and the brain: corticotropin-releasing hormone signaling

“…Arrestins were originally recognized for their ability to bind the activated GPCR and ‘arrest’ signaling via G proteins. However, over the years, it has been appreciated that arrestins not only prevent G protein activation but also have the capacity to function as multifunctional adaptor proteins that modulate endocytosis and transduce signals to multiple effector pathways ( 147 , 148 ). Arrestins critically regulate GPCR desensitization: they are recruited to phosphorylated GPCRs and initiate internalization by linking the receptor to the adaptor protein subunits of CCPs.…”