Dual Role of the β2-Adrenergic Receptor C Terminus for the Binding of β-Arrestin and Receptor Internalization

Cornelius Krasel, Ulrike Zabel, Kristina Lorenz, Susanne Reiner, Suleiman Al-Sabah, Martin J. Lohse
2008 Journal of Biological Chemistry  
Homologous desensitization of ␤ 2 -adrenergic and other G-protein-coupled receptors is a two-step process. After phosphorylation of agonist-occupied receptors by G-protein-coupled receptor kinases, they bind ␤-arrestins, which triggers desensitization and internalization of the receptors. Because it is not known which regions of the receptor are recognized by ␤-arrestins, we have investigated ␤-arrestin interaction and internalization of a set of mutants of the human ␤ 2 -adrenergic receptor.
more » ... energic receptor. Mutation of the four serine/threonine residues between residues 355 and 364 led to the loss of agonist-induced receptor-␤-arrestin2 interaction as revealed by fluorescence resonance energy transfer (FRET), translocation of ␤-arrestin2 to the plasma membrane, and receptor internalization. Mutation of all seven serine/threonine residues distal to residue 381 did not affect agonist-induced receptor internalization and ␤-arrestin2 translocation. A ␤ 2 -adrenergic receptor truncated distal to residue 381 interacted normally with ␤-arrestin2, whereas its ability to internalize in an agonist-dependent manner was compromised. A similar impairment of internalization was observed when only the last eight residues of the C terminus were deleted. Our experiments show that the C terminus distal to residue 381 does not affect the initial interaction between receptor and ␤-arrestin, but its last eight amino acids facilitate receptor internalization in concert with ␤-arrestin2.
doi:10.1074/jbc.m806086200 pmid:18801735 fatcat:hzcvibknh5cxxmrcepi3y26swq