Endocytosis of ligand-activated plasma membrane receptors has been shown
to contribute to the regulation of their downstream signaling. β-arrestins interact with
the phosphorylated tail of activated receptors and act as scaffolds for the recruitment of
adaptor proteins and clathrin, that constitute the machinery used for receptor
endocytosis. Visual- and β-arrestins have a two-lobe, immunoglobulin-like, β-strand
sandwich structure. The recent resolution of the crystal structure of VPS26, one of the
retromer subunits, unexpectedly evidenced an arrestin fold in this protein otherwise
unrelated to arrestins. From a functional point of view, VPS26 is involved in the
retrograde transport of the mannose 6-P receptor from the endosomes to the trans-Golgi
network. In addition to the group of true arrestins and Vps26, mammalian cells harbor a
vast repertoire of proteins that are related to arrestins on the basis of their PFAM Nter
and Cter arrestin-domains, which are named Arrestin Domain-Containing proteins
(ARRDCs). The biological role of ARRDC proteins is still poorly understood. The three
subfamilies have been merged into an arrestin-related protein clan.
This paper provides an overall analysis of arrestin clan proteins. The structures and
functions of members of the subfamilies are reviewed in mammals and model
organisms such as Drosophila, Caenorhabditis, Saccharomyces and Dictyostelium.
Keywords: Arrestins; Vps26; GPCR; Retromer; Trafficking; Endocytosis.
