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8.A.136. The Beta-Arrestin (ARRB) Family 

β-arrestins function in the desensitization of seven membrane spanning receptors (7MSRs, GPCRs, TC# 9.A.14), especially in the endocytosis and signaling of these receptors (Magalhaes et al. 2012). These functions reflect the ability of the beta-arrestins to bind signaling and endocytic elements, often in an agonist-dependent fashio n (Lefkowitz and Whalen 2004). One system leads to MAP kinase activation via beta-arrestin-mediated scaffolding of these pathways in a receptor-dependent fashion. The beta-arrestins are also found to be involved in the regulation of novel receptor systems, such as Frizzled and TGFbeta receptors as well as certain transporters such as ion channels and carriers (i.e., SLC9A5; the sodium/hydrogen exchanger, NHE5 (TC# 2.A.36.1.16). β-arrestin-1 acts as a scaffold for ADGRG2/CFTR complex formation in apical membranes, whereas specific residues of ADGRG2 confer coupling specificity for different G protein subtypes, the specificity of which is critical for male fertility (Zhang et al. 2018). 

References associated with 8.A.136 family:

Carroll, S.H., E. Zhang, B.F. Wang, K.B. LeClair, A. Rahman, D.E. Cohen, J. Plutzky, P. Patwari, and R.T. Lee. (2017). Adipocyte arrestin domain-containing 3 protein (Arrdc3) regulates uncoupling protein 1 (Ucp1) expression in white adipose independently of canonical changes in β-adrenergic receptor signaling. PLoS One 12: e0173823. 28291835
Gupta, M.K., M.L. Mohan, and S.V. Naga Prasad. (2018). G Protein-Coupled Receptor Resensitization Paradigms. Int Rev Cell Mol Biol 339: 63-91. 29776605
Han, S.O., R.P. Kommaddi, and S.K. Shenoy. (2013). Distinct roles for β-arrestin2 and arrestin-domain-containing proteins in β2 adrenergic receptor trafficking. EMBO Rep 14: 164-171. 23208550
Lefkowitz, R.J. and E.J. Whalen. (2004). β-arrestins: traffic cops of cell signaling. Curr. Opin. Cell Biol. 16: 162-168. 15196559
Magalhaes, A.C., H. Dunn, and S.S. Ferguson. (2012). Regulation of GPCR activity, trafficking and localization by GPCR-interacting proteins. Br J Pharmacol 165: 1717-1736. 21699508
Nabhan, J.F., H. Pan, and Q. Lu. (2010). Arrestin domain-containing protein 3 recruits the NEDD4 E3 ligase to mediate ubiquitination of the beta2-adrenergic receptor. EMBO Rep 11: 605-611. 20559325
Patwari, P., V. Emilsson, E.E. Schadt, W.A. Chutkow, S. Lee, A. Marsili, Y. Zhang, R. Dobrin, D.E. Cohen, P.R. Larsen, A.M. Zavacki, L.G. Fong, S.G. Young, and R.T. Lee. (2011). The arrestin domain-containing 3 protein regulates body mass and energy expenditure. Cell Metab 14: 671-683. 21982743
Shi, E., X. Zhou, D. Li, Y. Zhang, J. Yuan, and J. Zou. (2019). β-Arrestin2 regulates the rapid component of delayed rectifier K+ currents and cardiac action potential of guinea pig cardiomyocytes after adrenergic stimulation. Cell Mol Biol (Noisy-le-grand) 65: 132-137. 31880531
Zhang, D.L., Y.J. Sun, M.L. Ma, Y.J. Wang, H. Lin, R.R. Li, Z.L. Liang, Y. Gao, Z. Yang, D.F. He, A. Lin, H. Mo, Y.J. Lu, M.J. Li, W. Kong, K.Y. Chung, F. Yi, J.Y. Li, Y.Y. Qin, J. Li, A.R.B. Thomsen, A.W. Kahsai, Z.J. Chen, Z.G. Xu, M. Liu, D. Li, X. Yu, and J.P. Sun. (2018). Gq activity- and β-arrestin-1 scaffolding-mediated ADGRG2/CFTR coupling are required for male fertility. Elife 7:. 29393851