Small ubiquitin-like modifier modification of arrestin-3 regulates receptor trafficking.
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.
Mesh Terms:
Animals, Arrestins, Binding Sites, Cattle, Cell Line, Endocytosis, Humans, Protein Processing, Post-Translational, Receptors, Adrenergic, beta-2, Receptors, G-Protein-Coupled, SUMO-1 Protein, Sumoylation
Animals, Arrestins, Binding Sites, Cattle, Cell Line, Endocytosis, Humans, Protein Processing, Post-Translational, Receptors, Adrenergic, beta-2, Receptors, G-Protein-Coupled, SUMO-1 Protein, Sumoylation
J. Biol. Chem.
Date: Feb. 04, 2011
PubMed ID: 21118812
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