Small ubiquitin-like modifier modification of arrestin-3 regulates receptor trafficking. J Biol Chem 2011 Feb 04;286(5):3884-93
Date
12/02/2010Pubmed ID
21118812Pubmed Central ID
PMC3030389DOI
10.1074/jbc.M110.152116Scopus ID
2-s2.0-79952777210 (requires institutional sign-in at Scopus site) 43 CitationsAbstract
Nonvisual arrestins are regulated by direct post-translational modifications, such as phosphorylation, ubiquitination, and nitrosylation. However, whether arrestins are regulated by other post-translational modifications remains unknown. Here we show that nonvisual arrestins are modified by small ubiquitin-like modifier 1 (SUMO-1) upon activation of β(2)-adrenergic receptor (β(2)AR). Lysine residues 295 and 400 in arrestin-3 fall within canonical SUMO consensus sites, and mutagenic analysis reveals that Lys-400 represents the main SUMOylation site. Depletion of the SUMO E2 modifying enzyme Ubc9 blocks arrestin-3 SUMOylation and attenuates β(2)AR internalization, suggesting that arrestin SUMOylation mediates G protein-coupled receptor endocytosis. Consistent with this, expression of a SUMO-deficient arrestin mutant failed to promote β(2)AR internalization as compared with wild-type arrestin-3. Our data reveal an unprecedented role for SUMOylation in mediating GPCR endocytosis and provide novel mechanistic insight into arrestin function and regulation.
Author List
Wyatt D, Malik R, Vesecky AC, Marchese AAuthor
Adriano Marchese PhD Professor in the Biochemistry department at Medical College of WisconsinMESH terms used to index this publication - Major topics in bold
AnimalsArrestins
Binding Sites
Cattle
Cell Line
Endocytosis
Humans
Protein Processing, Post-Translational
Receptors, Adrenergic, beta-2
Receptors, G-Protein-Coupled
SUMO-1 Protein
Sumoylation
