High impact information on ARRB1

• Here we report that beta-arrestin and arrestin-3, but not visual arrestin, promote beta2AR internalization and bind with high affinity directly and stoichiometrically to clathrin, the major structural protein of coated pits [1].
• Ultimately the receptor undergoes internalization, and although the molecular mechanism is unclear, receptor phosphorylation and beta-arrestin binding have been implicated in this processs [1].
• The ability of a system to regulate its responsiveness in the presence of a continuous stimulus, often termed desensitization, has been extensively characterized for the beta2-adrenergic receptor (beta2AR). beta2AR signalling is rapidly attenuated through receptor phosphorylation and subsequent binding of the protein beta-arrestin [1].
• These results show that beta-arrestin functions as an adaptor in the receptor-mediated endocytosis pathway, and suggest a general mechanism for regulating the trafficking of G-protein-coupled receptors [1].
• High-affinity binding sites for phosphoinositides in beta-arrestin (arrestin2) and arrestin3 (beta-arrestin2) were identified, and dissimilar effects of phosphoinositide and inositol phosphate on arrestin interactions with clathrin and receptor were characterized [2].

Biological context of ARRB1

• Subsequent binding site localization studies indicated that the interaction of beta-arrestin with the M3-MR peptide required both the amino (Gly308-Leu368) and carboxyl portions (Lys425-Leu497) of the receptor subdomain [3].
• Our two-dimensional isoelectric focusing gels using rat spinal cord and heart tissues demonstrate isoelectric heterogeneity of rat beta-arrestin-1, suggesting that beta-arrestin-1 is subject to post-translational modification unlike beta-arrestin-2 [4].
• In photoreceptor cells, their specific localization in the synaptic terminals and plexiform layer suggests a role of beta-arrestin in synaptic transmission [5].
• In other ocular tissues, the presence of beta-arrestin may be related either to adrenergic signal transduction or to signal transduction mediated by other G-protein-coupled receptors [5].
• There is significant homology between amino acid sequences of human thyroid arrestin and human retinal arrestin (63%) and bovine beta-arrestin (74%), respectively [6].

Anatomical context of ARRB1

• Differential expression of alternative splice variants of beta-arrestin-1 and -2 in rat central nervous system and peripheral tissues [4].
• These results show that endogenous beta-arrestin participates in cell-free desensitization of agonist-dependent LH/CG R-stimulated AC activity in follicular membranes by interacting directly with the 3i loop of the receptor, thereby preventing Gs activation [7].

Associations of ARRB1 with chemical compounds

• beta-arrestin-dependent desensitization of luteinizing hormone/choriogonadotropin receptor is prevented by a synthetic peptide corresponding to the third intracellular loop of the receptor [7].
• The nonvisual arrestins, beta-arrestin and arrestin3, but not visual arrestin, bind specifically to a glutathione S-transferase-clathrin terminal domain fusion protein [8].
• Although the insertion of a Gly residue (absent in arrestins but present in the putative phosphate-binding site of ataxin-7) disrupts the function of visual arrestin-ataxin-7 chimera, it enhances the function of beta-arrestin-ataxin-7 chimera [9].

Other interactions of ARRB1

• Beta-arrestin acts as a clathrin adaptor in endocytosis of the beta2-adrenergic receptor [1].
• However, phosphorylation alone seems insufficient to inhibit receptor function, and it has been proposed that the inhibition is mediated, following receptor phosphorylation, by the additional proteins beta-arrestin in the case of beta-adrenergic receptors and arrestin in the case of rhodopsin [10].

Analytical, diagnostic and therapeutic context of ARRB1

• Immunofluorescence microscopy of intact cells indicates an agonist-dependent colocalization of the beta2AR and beta-arrestin with clathrin [1].
• In this report we show the presence of two alternatively spliced forms of beta-arrestin-1 in several rat tissues using both reverse transcription-polymerase chain reaction and Western immunoblot [4].
• The sequence of PCR products from bovine retina and RPE cells was identical with the bovine beta-arrestin mRNA [5].
• Recruitment of beta-arrestin 1 in response to receptor activation was demonstrated by confocal microscopy [11].

References