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).