Table 1 Comparison of β-arrestin1 and β-arrestin2.
β-arrestin1 | β-arrestin1 and β-arrestin2 | β-arrestin2 | |
|---|---|---|---|
Structure | Does not contain a C-terminal NES. | Share 78% sequence similarity1,2. Contain an N-terminal NLS for nuclear import26,28. | Contains a C-terminal NES, allowing for nuclear-cytoplasmic shuttling29. |
Expression patterns | Up to 10× more abundant in the brain than β-arrestin221. | Universally expressed in most mammalian cell types and tissues, and highly expressed in the brain12,13,20. | |
Protein concentration increases with age in the rat brain21. | Expression patterns are influenced by age. | Protein concentration decreases with age in the rat brain21, with an average immunodensity decrease of 3–5% per decade in the human brain22. | |
Similar expression in the prefrontal cortex and striatum in the rat brain24. | Equal expression in striatal MSNs of direct and indirect dopamine pathways23. High expression in the pyramidal cells of the cortex and hippocampus20. | Higher expression in the prefrontal cortex compared to striatum in the rat brain24. | |
Class A GPCR interactions | Highly involved in the regulation of Class A GPCR signaling while similarly recruited by Class B GPCRs27. | Greater affinity for class A GPCRs compared to that of β-arrestin127. | |
There is very little research on the β-arrestin1-β2AR interaction despite the known high affinity between β-arrestin2 and the β2AR. | Most β2AR ligands trigger a similar degree of β-arrestin recruitment to the β2AR180. | Tenfold more efficient at internalizing the β2AR, and 100-fold greater amount of β-arrestin1 is needed to match β-arrestin2-driven β2AR internalization37. Significantly higher binding affinity for the β2AR than β-arrestin136,37. | |
Preferentially interacts with the D2R dopamine receptor isoform38. | Interact with D1R and D2R to participate in dopaminergic signaling38,39. | Preferentially interacts with the D1R dopamine receptor isoform39. | |
Knockdown suppresses adenylyl cyclase activity46 High internalizing dOR agonists facilitate β-arrestin1 recruitment to the dOR47. β-arrestin1 plays a greater role in mOR internalization compared to β-arrestin246. | Interact with opioid family receptors (mOR and dOR) and play a potentially neuroprotective role181. | Knockdown enhances adenylyl cyclase activity46 Low-internalizing dOR agonists facilitate β-arrestin2 recruitment to the dOR47. | |
Class B GPCR interactions | Equal interaction with the AT1aR with equal recruitment and binding affinity, albeit with slightly different conformations49. | Causes a greater affinity shift in response to certain agonists compared to β-arrestin149. | |
Preference for binding to and stabilizing the “hanging” PTH1R conformation51. | Equally recruited to the mAChR in response to ligand activation50 Equally recruited to the active PTH1R51. | Preference for binding to and stabilizing the “core” PTH1R conformation51. |
