Ascidian arrestin (Ci‐arr), the origin of the visual and nonvisual arrestins of vertebrate

Arrestin is one of the key proteins for the termination of G protein signaling. Activated G protein‐coupled receptors (GPCRs) are specifically phosphorylated by G protein‐coupled receptor kinases (GRKs) and then bind to arrestins to preclude the receptor/G protein interaction, resulting in quenching of the following signal transduction. Vertebrates possess two types of arrestin; visual arrestin expressed exclusively in photoreceptor cells in retinae and pineal organs, and β‐arrestin, which is expressed ubiquitously. Unlike visual arrestin, β‐arrestin contains the clathrin‐binding domain at the C‐terminus, responsible for the agonist‐induced internalization of GPCRs. Here, we isolated a novel arrestin gene ( Ci‐arr ) from the primitive chordate, the ascidian Ciona intestinalis larvae. The deduced amino acid sequence suggests that Ci‐Arr be closely related to vertebrate arrestins. Interestingly, this arrestin has the feature of both visual and β‐arrestin. Whereas the expression of Ci‐arr was restricted to the photoreceptors in the larvae similarly to visual arrestin, the gene product, containing the clathrin‐binding domain, promoted the GPCR internalization in HEK293tsA201 cells similarly to β‐arrestin. The phylogenetic tree shows that Ci‐Arr is branched from a common root of visual and β‐arrestins. Southern analysis suggests that the Ciona genome contains only one gene for the arrestin family. These results suggest that the visual and β‐arrestin genes were generated by the duplication of the prototypical arrestin gene like Ci‐arr in the early evolution of vertebrates.