The role of arrestins in development

Abstract

β-Arrestins are versatile scaffolding proteins that are involved in orchestrating a large number of signaling cascades. Because β-arrestin 1 and β-arrestin 2 are individually dispensable during development, it has long been assumed that β-arrestins do not play an important role during embryogenesis. Nonetheless, there is growing evidence from both invertebrate and vertebrate animal models that β-arrestins are integral regulators of developmental pathways. They are involved in diverse processes such as early hematopoiesis, establishment of axial development axes, cell convergence and extension movements leading to axial elongation, musculoskeletal and craniofacial development, cell proliferation, and neuronal development. Most of the developmental roles of arrestins involve interactions with or regulation of novel non-G protein-coupled receptor partners, such as atypical seven-transmembrane receptors, small G proteins, and nuclear transcription factors, revealing surprising diversity in arrestin function. In contrast to their largely overlapping roles in G protein-coupled receptor desensitization and internalization, study of the role of arrestins in development has demonstrated marked functional specialization of the β-arrestin 1 and 2 isoforms.