βArrestins:: New roles in regulating heptahelical receptors' functions

The last few years have seen a marked expansion in appreciation of the diversity of roles played by the Arrestins in regulating GPCR functions. Originally discovered as molecules that desensitize such receptors, the roles of beta Arrestins have expanded to include acting as signalling adapters or intermediates that recruit other key molecules to the GPCRs in an agonist-regulated fashion. For example, interactions with components of the endocytic machinery, such as clathrin, the adapter protein AP-2 and the N-ethylinaleimide sensitive fusion protein (NSF), demonstrate the ability of beta Arrestins to act as adapters to facilitate the clathrin-mediated endocytosis of certain members of the GPCR family. beta Arrestins have also been shown to serve as signalling molecules. The Ras-dependent activation of ERK1/2 may involve the beta Arrestin-dependent recruitment of c-Src to the beta2-adrenergic receptor (beta2-AR). More recently, beta Arrestins have been shown to act as molecular scaffolds that coordinate the assembly of certain MAP kinase complexes that lead to the stimulation of either ERK1/2 or JNK3. Finally, long-term accumulation of arrestin-rhodopsin complexes, in photoreceptor cells has been shown to trigger apoptosis. (C) 2001 Elsevier Science Inc. All rights reserved.