Arrestins: ubiquitous regulators of cellular signaling pathways

The arrestin family has four members in mammals: arrestin1 (called visual or rod arrestin in some species, and previously called S-antigen or 48 kDa protein), arrestin2 (also known as β-arrestin or β-arrestin1), arrestin3 (β-arrestin2) and arrestin4 (cone arrestin or X-arrestin). Structurally and functionally the family can be subdivided into two subfamilies: visual or sensory (arrestin1 and arrestin4) and non-visual (arrestin2 and arrestin3) [1]. Fish and amphibians have a rod arrestin, a cone arrestin and at least one non-visual arrestin; insects have at least two sensory arrestins and one non-sensory arrestin (called Kurtz in Drosophila melanogaster), whereas other invertebrates (such as Caenorhabditis elegans) and protochordates (such as Ciona intestinalis) have only one arrestin homolog. Chromosomal locations and accession numbers are shown in Tables 1 and 2, respectively.In vertebrates, arrestins are encoded by large (13-50 kilobases) genes containing 14-17 exons, some of which are only 10 nucleotides long [2,3]. This multi-exon structure appears to be ancient, as the sole arrestin in the protochordate C. intestinalis is encoded by 13 exons, with the positions of nine introns corresponding to those in bovine rod arrestin (arrestin1) [4]. The arrestin gene in C. elegans has ten exons [5], whereas the genes in D. melanogaster are simpler, having only three or four exons [6]. The positions of five introns are identical in C. elegans, C. intestinalis and bovine rod arrestin, suggesting that they were acquired by a common ancestor gene. The exons do not correspond to known structural elements of arrestins, which consist of two domains and a variable carboxy-terminal tail [7-9], with one interesting exception: one of the exons conserved from C. elegans to mammals contains the phosphate-binding motif homologous to a motif in ataxin-7, a protein mutated in olivopontocerebellar atrophy with retinal degeneration [10]. The multi-exon structure of vertebrate arrestins giv