Beta-Arrestins: 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 betaArrestins in regulating GPCR functions. Originally discovered as molecules that desensitize such receptors, the roles of betaArrestins 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-ethylmaleimide sensitive fusion protein (NSF), demonstrate the ability of betaArrestins to act as adapters to facilitate the clathrin-mediated endocytosis of certain members of the GPCR family. BetaArrestins have also been shown to serve as signalling molecules. The Ras-dependent activation of ERK1/2 may involve the betaArrestin-dependent recruitment of c-Src to the beta2-adrenergic receptor (beta2-AR). More recently, betaArrestins 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.
McDonald
P H
PH
Department of Medicine, Howard Hughes Medical Institute, Duke University Medical Center, Box 3821, Durham, NC 27710, USA.
Lefkowitz
R J
RJ
D000818:Animals; D019390:Arrestins / Q000502:physiology*; D015536:Down-Regulation; D004705:Endocytosis; D020962:Heterotrimeric GTP-Binding Proteins / Q000378:metabolism*; D020935:MAP Kinase Signaling System; D046911:Macromolecular Substances; D008954:Models, Biological; D011956:Receptors, Cell Surface / Q000502:physiology*; D000071557:beta-Arrestins
D019390:Arrestins; D046911:Macromolecular Substances; D011956:Receptors, Cell Surface; D000071557:beta-Arrestins; D020962:Heterotrimeric GTP-Binding Proteins